Abstract
The second and third decades of the twenty-first century are marked by a flourishing of space technology which may soon realise human aspirations of a permanent multiplanetary presence. The prevention, control and management of infection with microbial pathogens is likely to play a key role in how successful human space aspirations will become. This review considers the emerging field of medical astro-microbiology. It examines the current evidence regarding the risk of infection during spaceflight via host susceptibility, alterations to the host’s microbiome as well as exposure to other crew members and spacecraft’s microbiomes. It also considers the relevance of the hygiene hypothesis in this regard. It then reviews the current evidence related to infection risk associated with microbial adaptability in spaceflight conditions. There is a particular focus on the International Space Station (ISS), as one of the only two crewed objects in low Earth orbit. It discusses the effects of spaceflight related stressors on viruses and the infection risks associated with latent viral reactivation and increased viral shedding during spaceflight. It then examines the effects of the same stressors on bacteria, particularly in relation to changes in virulence and drug resistance. It also considers our current understanding of fungal adaptability in spaceflight. The global public health and environmental risks associated with a possible re-introduction to Earth of invasive species are also briefly discussed. Finally, this review examines the largely unknown microbiology and infection implications of celestial body habitation with an emphasis placed on Mars. Overall, this review summarises much of our current understanding of medical astro-microbiology and identifies significant knowledge gaps.
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1 Introduction
The emergence and dissemination of infectious disease has been a regular occurrence throughout human history and has led to pivotal societal, economic, and technologic changes. In premodern societies many infectious diseases such as cholera, polio, the plague, smallpox and typhus were endemic and/or caused periodic major epidemics resulting in extensive death, disability and societal disruption.1 Spread of infection was facilitated by conflict, colonisation, war, poverty, poor hygiene, inadequate sanitation, and absence of current technologies for detection, prevention and management of infection including modern-day medical advancements such as antibiotics and vaccines.2 Despite advances in the understanding and control of infectious disease, human society remains vulnerable to the emergence and dissemination of infection. New emerging infectious diseases (EIDs)MN1 have become increasingly recognised in recent decades.3 The rise of EIDs is likely related to population expansion, changes in agricultural practices to more intensive food production, climate change, urbanisation, an unprecedented level of global connectedness and complex/concentrated healthcare systems. These factors are also enabling infectious disease outbreaks to rapidly disseminate within the human population, allowing minimal time for effective containment of emerging infections.4,5 This continuing threat is illustrated by the dissemination of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), Mpox, Human Immunodeficiency Virus (HIV) and Carbapenemase-Resistant Enterobacterales (CRE) amongst others.6,7,8,9 Globalisation has also been associated with environmental risks related to invasive species (i.e., organisms not native in a particular area).10 The environmental and biodiversity impact of invasive macroMN2 and mega faunaMN2 and flora is readily apparent.11,12 The phenomenon of microbial invasive species is much less apparent and less well studied, but by extrapolation from the dissemination of antimicrobial resistant organisms (AROs) it is likely that globalisation also contributes to a rapid change and homogenisation in the global microbiome.13 In this context, careful consideration must be given to potential risks of emergence and spread of invasive microbial species associated with space travel and multi-planet settlement in the coming decades.
Space travel has so far been reserved for relatively few; predominantly specially selected and trained astronauts. The moderating agencies [e.g., National Aeronautics and Space Administration (NASA)] apply a series of measures to manage risk of infection such as those described in NASA’s Health Stabilisation Programme (HSP).14 In the coming decades, a shift towards space travel and multi-planetary space settlement is expected, with permanent human presence planned on the Moon and Mars within the next two decades.15 By 2050, SpaceX is estimating that thousands of people could be living and working on Mars. Schedules for smaller research-based outposts of 1000–2500 inhabitants are also anticipated for the Moon within the same timeframe. Regardless of the timeline feasibility of these projections, an extended permanent human space presence is anticipated within the next few decades.16 The challenges from a microbiological and infectious disease perspective are multifaceted. They firstly entail the protection of the space traveller from infection during spaceflight. Infection may originate from their own microbiome (e.g., reactivation of latent microorganisms),17 the microbiome of other space travellers or the environment.18 At the present time the environment is primarily the interior of constructed spacecrafts of terrestrial origin. Exposure in that context is expected to be to terrestrial organisms or to organisms of terrestrial origin that have been altered by selective forces encountered during spaceflight.19 In the future, when plans to populate the surface of other celestial bodies proceed there is a potential risk of exposure to extant extra-terrestrial microorganisms, if such life exists.20 Furthermore, such an encounter would have uncharted interactions with terrestrial microbial life forms and depending on genomic compatibility there might be a potential for terrestrial microorganisms to incorporate genetic elements of such extant organisms.
The larger overall challenge is the protection of global public health and the global environment from risks associated with return of vehicle, materials, and travellers to Earth. The more immediate risk could relate to the potential to introduce pathogenic and drug resistant invasive microorganisms that have adapted within a spacecraft environment and are capable of dissemination on Earth. The more remote possibility is the accidental introduction of extra-terrestrial microorganisms into Earth systems. The likelihood of introduction and escape of microorganisms that are well adapted to Earth environments and are harmful to human, animal or plant health (pathogenic) or to the environment (invasive species)MN3 is deemed to be low.21 On the other hand, the consequences of such introduction would be severe for public and environmental health as well as for the reputation and sustainability of space exploration. Furthermore, a permanent human presence on other celestial bodies (e.g., Mars) would certainly introduce terrestrial microorganisms to those settings.22,23 In the event of human travel, the introduction of terrestrial microorganisms is unavoidable as humans travel with their microbiome.24 Sustained containment is likely to be unmanageable. If those extra-terrestrial environments are capable of sustaining growth of terrestrial microorganisms, human travel and habitation will almost inevitably result in dissemination of those organisms that can grow and subsequently adapt and diversify from seeded organisms to the new environment.
So far, our overall understanding of the microbiology and infectious disease related risks associated with a multi-planetary presence and prolonged spaceflight is very limited. The planned interconnectedness of Earth with orbital and celestial habitats requires public health considerations for both the outpost inhabitants and the terrestrial population alike. Our current understanding is guided by pioneering studies conducted mostly on the ISS or on microgravity and Mars simulating scenarios on Earth.25,26 Most terrestrial experiments have set limitations in their inability to simulate the type and amount of UV and cosmic ionising radiation encountered in space.27 This provides a background for review and interpretation of the literature in relation to microbiology and infection in the context of space travel and space settlement. This evidence base is growing but is currently limited. There overall appear to be the following two main considerations in relation to medical astro-microbiology: (i) space travel and (ii) celestial body outposts, each with unique risks and challenges (Fig. 1).
2 Spaceflight
Spaceflight with our current technological capabilities exposes life (acellular, unicellular and multicellular) to three main physical stressors that differ from those encountered on Earth. These are microgravity, increased radiation (UV and cosmic/ionising)MN4 and circadian disruption. In this review we will focus on the effects of microgravity and radiation. The effects of spaceflight to circadian rhythm and its evident association with astronaut health and microbiomes has been studied and reviewed elsewhere.28,29,30 Other environmental factors such as space vacuum and thermal extremes are mitigated by our current spacecraft designs. Exposure of a host, in this case an astronaut, to a microbe may result in (1) failure for the organism to establish itself on the host, (2) colonisation of the host or (3) infection.31 The factors that determine the outcome are complex dynamic interactions dependent on the characteristics of the microbe, the host and other microbial elements of the host microbiome. The interaction may also contribute to heritable changes in a microbe that could influence its ability to transmit to and colonise or infect other hosts.32 A full understanding of the implications of space travel in relation to infection risk therefore requires an understanding of space travel associated effects on both human and microbial physiology. Furthermore, it could be speculated that stressors of spaceflight could cause an alteration to the incubation period of infectious diseases, though such effects are currently unmapped.
Throughout the over 20 years of permanent human presence in low Earth orbit, the effects of spaceflight to humans have been relatively well documented.33,34 A typical ISS expedition lasts about 6 months, although much longer stays in space have been recorded such as the one achieved by astronaut Scott Kelly and cosmonaut Mikhail Kornienko who spent 340 days in low-Earth orbit with scientists performing medical experiments (e.g., NASA's twins study). They launched on 27 March 2015 on Soyuz TMA-16M along with Gennady Padalka. The longest recorded stay in low-Earth orbit has been achieved by cosmonaut Valery Polyakov who remained in spaceflight for 438 days between 1994–1995.35 This compares to a 3-day duration for an one-way flight to the Moon and a 9-month duration for an one way flight to Mars.36,37,38 Beyond that timeframe, the effects of spaceflight on human physiology are unknown and therefore for longer flights to desirable locations with settlement prospects such as Jupiter’s moon Europa (628.3 million km distance, ~3 years of spaceflight) a better understanding of spaceflight associated effects to humans is required. By contrast, the effects of spaceflight on microbial life and the host microbiome have been studied and understood to a lesser extent.
2.1 Host Susceptibility During Spaceflight
Spaceflight has been observed to induce alterations to human physiological functions for a variety of different systems. The immune and musculoskeletal systems appear to be the most susceptible to the stressors induced by spaceflight.39,40 A comprehensive review on the effects of spaceflight on the human body has been published previously.41 Due to its direct involvement in immunity and infection we will focus on the immune system. An overall dysregulation of the immune system in individuals undergoing spaceflight has been observed to include altered function and dispersion of different components including cytokines.42 Both the bone marrow and thymus are adversely affected by microgravity and space radiation with an overall impairment of lymphopoiesisMN5 which could lead to a disturbance of acquired immunity.43 Studies have also identified an increased incidence rate of hypersensitivities in crew members on board the ISS which may partially be a result of immune system impairment, possibly through a reported Th2 cytokineMN6 sensitisation.44 Rashes are the most reported clinical events on board the ISS with an incidence rate of over 25-fold higher than that reported on Earth.45 Diagnoses also include eczema, psoriasis and contact dermatitis amongst others, with antihistamines being one of the most prescribed in-flight medications.46 The observed immune system dysregulations are also known to be linked with latent viral reactivation during spaceflight. A recent observation relates to a link between an increased level of plasma cytokines in astronauts and a high incidence rate of latent Herpesviridae reactivation.47 Several incidents of Herpesviridae reactivation amongst the ISS crew have already been reported.48 It is important to note that every study conducted so far, agrees that the immune alterations during spaceflight are acute, and they only persist for the duration of the mission. Of note, most of the studies assessing the effects of spaceflight on the immune system have been conducted using rodent models. The exact extent of the effects spaceflight conditions has on the human immune system is not fully understood at this time.
2.2 The Closed Habitat Microbiome
Spaceflight by humans (or animals) currently occurs in hermetically sealed systems such as the ISS. This environment cannot be maintained as sterile because humans are hosts to a diverse microbiome that accompanies space travellers.49 Each traveller has a distinctive microbiome and therefore introduces new elements of the terrestrial microbiome into the ISS environment.50 Nevertheless, the diversity of microbes in the ISS is narrow compared to the microbial diversity of non-sealed terrestrial environments.51 This relatively narrow microbiome base is subject to selective pressures that differ in several aspects from those prevailing in terrestrial environments. The impacts of microgravity and of increased radiation (UV and ionising) exposure are widely recognised and often considered to predominate.52,53 However, there are other factors that may be equally significant in shaping change in organisms of terrestrial origin within space vehicles. Surface materials on which organisms grow as well as the composition of the atmosphere and the humidity of the spaceflight environment differ from many terrestrial environments in terms of quality and in lack of variation.54 The use of intensive surface cleaning and disinfection protocols are also likely to narrow the spacecraft microbiome and select for organisms with intrinsic or acquired resistance to the agents used.55,56 Lastly, the relative narrowness of the microbiome itself is likely to be a significant factor in shaping the microbiome from organisms that are introduced.
2.3 Effect of Spaceflight to the Human Microbiome
The human microbiome has a widely recognised role in maintaining optimal human physiological functions. The microbiome relates to the compilation of different communities of bacteria, archaea, fungi and viruses whose composition is dynamic and influenced by environmental conditions.57 Disturbances to a healthy microbiome (dysbiosis) has been extensively linked with systemic diseases such as depression,58 Inflammatory Bowel Disease (IBD)59 and age-related neurological diseases such as Alzheimer’s disease amongst others.60 Gut and oral microbiome dysbiosis have also been extensively linked with an increased risk of infection including microbial translocationMN7 and bacteraemiaMN8.8,61,62 Two well-established opportunistic infections caused by microbiome dysbiosis are these induced by Clostridium dificile (colitis) and Candida albicans (candidiasis).63,64 Additionally, the gut microbiome contributes to the maintenance of the intestinal wall. Gut dysbiosis can contribute to disruption of the gut barrier resulting in hyperpermeability of the gut walls or gut leakiness.65 This hyperpermeable state causes gastrointestinal (GI) tract dysfunction and can allow for translocation of both microbes and microbial products. Movement of microbes out of the gut and into systemic circulation has been associated with disorders including celiac disease.66 As with the human immune system, the human microbiome has been observed to be susceptible to space-related environmental stressors. A study conducted in a Hindlimb Unloading (HU), Dextran Sulphate Sodium (DSS) colitis induced mouse model in simulated microgravity conditions revealed an overall predisposition to colitis.67 When compared to the ground control mice, the mice exposed to microgravity had an associated early onset of colitis, a fourfold increase of segmented filamentous bacteria, more than a twofold decrease in regulatory T cells (Treg) absolute numbers as well as a reported twofold increase in colonic IL-1β and circulating neutrophils. The overall results of this and other studies utilising murine models68 suggest that both the rodent gut microbiome and the innate immune system, adversely respond to simulated microgravity contributing to a pro-inflammatory shift in the gut. The association of these findings with human physiology warrants further investigation. Studies examining the impact of spaceflight directly on the astronaut’s microbiome have also been attempted. A change in abundance of certain genera and species in the skin, nose, tongue and gastrointestinal tract of astronauts, which is usually a sign of dysbiosis, has been reported.33,69 Some signs of increased frequency of antimicrobial resistance (AMR) markers during spaceflight across five body areas including the skin and the mouth has been noted in one study.33 The AMR markers mostly related to tetracycline and erythromycin resistance. It needs to be highlighted that, so far human based microbiome studies during spaceflight have a very limited sample size (n = 4–9) and therefore statistical inference is difficult. An overall link between microbiome changes and the observed immune system impairment during spaceflight seems highly likely and larger studies are required when human space presence is extensive and larger cohorts are available. Furthermore, an association between the microbiome changes, impairment in immune system function and excessive hygiene could also be explored.
2.4 The Hygiene Hypothesis
The original version of the hygiene hypothesis related to the suggestion that early-life exposure to infections prevents the development of allergies.70 The current description goes beyond that and includes non-pathogenic microorganisms (i.e., commensals and symbionts)MN9 and expands to any inflammatory disease.71 A demonstration of the hygiene hypothesis relates to a significantly reduced risk for developing childhood asthma amongst children with early exposure to livestock in farm environments.72 Meta-analysis has shown an overall 25% reduction in asthma prevalence amongst children with early farm exposure.73 The reason behind this association is complex and it likely involves the effects of endotoxins, microbial diversity, and single pathogens. As mentioned before, pioneering astronaut-based microbiome studies have noted changes in both the skin and the gut microbiome amongst others, disturbances of which are known to be linked with inflammatory disease and skin pathologies. Microgravity, increased radiation (UV/ionising), stress and circadian rhythm disruptions associated with spaceflight could all be contributing to both the spaceflight associated microbiome dysbiosis and the immune dysregulation.33 Diet is generally well monitored during spaceflight, and it might be less of contributing factor to microbiome dysbiosis.74 A question that remains to be addressed relates to whether the highly clean environment of the ISS is another contributing factor to the observed microbiome changes and noted immune system dysregulation. Suggestions that an adoption of a more “natural” spaceflight environment could mitigate some of these health risks based on the hygiene hypothesis have been made previously and are well supported by literature.75 Given one of the main aims of space exploration is to identify microbial extra-terrestrial life, ultra-hygienic protocols during spaceflight have a rationale. Further research is required to elucidate the health benefits of a more “natural” spaceflight environment for the crew. A balance between crew’s health and “ultra- cleanliness” could then be achieved.
2.5 Effect of Spaceflight on Microbial Species
Viral, bacterial and fungal agents are known to have their properties altered during spaceflight. Spaceflight conditions have been noted to have significant effects on microbial properties including a reported enhanced pathogenic ability for some bacterial and fungal species in in-vivo infection models. Overall, the best example we have in terms of understanding microbial properties in space relate to the experiments conducted throughout the over 20 years of the ISS presence in low Earth orbit. Although several studies have been conducted on viral, fungal and bacterial species there appears to be a notable lack of research on the adaptation of human disease associated parasites such as Giardia lamblia and Cryptosporidium parvum to spaceflight conditions.
2.5.1 Viruses
A review of our current understanding in spaceflight virology was recently published.76 So far, at least two studies using culture independent methods have included viruses aboard the ISS.54,77 NASA’s twin study provided a thorough assessment of gut microbiome changes associated with spaceflight capturing both the single-stranded (ss) and double-stranded (ds) DNA virome.77 The twin study identified characteristic overall microbiome changes in composition and function associated with spaceflight. These changes could be due to isolation and dietary changes rather than spaceflight induced. Based on NASA’s shotgun metagenomics-based study EXTREMOPHILES, the ISS DNA viromeMN10 appears to be dominated by bacteriophages (>95% of all viral reads).54 The remaining viral metagenomic reads belong to animal/human viruses. The most abundant DNA virus appeared to be the Enterobacterales bacteriophage Microvirus (68.84% relative abundance) followed by the bacteriophage family Siphoviridae (22.60% relative abundance). The most abundant non-bacteriophage related viral genera appeared to be Mastadenovirus which uses humans and other mammals as natural hosts (1.46% relative abundance). The human Mastadenovirus (HAdVs) is usually transmitted via the faecal–oral route and can cause a broad spectrum of diseases included pulmonary infection and gastroenteritis.78 Viruses of the family Herpesviridae were also identified including Roseolivirus (0.01% relative abundance) and Varicellovirus (0.09% relative abundance). Viruses of the genera Roseolivrus and Varicellovirus are well documented human pathogens and crucially can be transmitted by aerosolised respiratory droplets.79,80 There are two main limitations in studies utilising shotgun metagenomic sequencing for examining viruses: (i) most DNA shotgun metagenomics protocols target dsDNA and, therefore, ss-DNA viruses are excluded, and (ii) the absence of metatranscriptomic based studies which leads to a complete absence of information on RNA viruses. A mapping of the ISS ss-DNA and RNA virome would, therefore, be an important step in enhancing our ISS microbiome understanding. It has been suggested that the virome of closed environments such as buildings is largely originating from the outside environment with human presence strongly influencing the viral community of such spaces.54,81 For the ISS, the main sources of viruses are humans and equipment cross-contamination.
Furthermore, respiratory-based pathogen transmission during spaceflight requires special consideration and careful planning. In terms of airborne transmission of viruses in sealed systems, clarity is required in the use of the terms ‘droplets’ and ‘aerosols’, as these terms are sometimes used interchangeably. A scientific gold standard for an emission size cut-off between the two does not currently exist. Both the World Health Organisation (WHO) and the Centre for Disease Control (CDC) recommendations adopt a 5 μm cut-off to distinguish between the two categories.82,83 Emissions >5 μm in diameter are termed as droplets and the ones <5 μm in diameter are termed as aerosols. There are well-supported suggestions that this cut-off is not based on solid scientific evidence and is, therefore, misleading,84 but this is beyond the scope of this review. Aerosol deposition in human lungs is largely driven by gravitational sedimentation.85 Studies looking at the aerosol deposition of 0.5- to 3 μm particles in both microgravity and hypergravityMN11 during parabolic flights identified an increased level of aerosol deposition in human lungs under hypergravity conditions.85In microgravity conditions, the same study revealed that aerosols deposit peripherally (alveolar deposition) in the lung, beyond the protective effect of the mucociliary clearance system, increasing the risk for the establishment of a respiratory infection. Under normal conditions, respiratory droplets (>5 μm) deposit mainly in the upper and large airways.86 In microgravity-induced conditions (during parabolic flights), 5 μm diameter radiolabelled particles (resembling respiratory droplets) deposited in the central airways, where clearance mechanisms remain effective.87 Furthermore, the same study reported a reduction in 5 μm diameter particle deposition under microgravity conditions. Respiratory droplets are known to follow a gravity-influenced, semi-ballistic trajectory, and they usually settle no more than 2 meters from the source.84 It can, therefore, be hypothesized that microgravity would significantly alter the respiratory droplet trajectory, increasing its deposition range. Further studies are required to shed light into the fate of respiratory droplets under microgravity conditions as this is one of the main modes of human to human transmission for airborne bacteria and viruses.84 The effect of microgravity on the respiratory cilia and mucous production also remains unclear, alterations on which could also increase the risk of infection. Overall, in contrast with the immune system, the human respiratory system appears to remain unaffected in microgravity conditions and there is no known overall degradation in lung function.88 From what is known so far, an increased infection risk due to reduced lung function is not anticipated and the transmission risk relates to the effects of microgravity on aerosol transmission and deposition.
It is well documented that latent viruses, particularly of the family Herpesviridae, are commonly reactivated in astronauts on the ISS. This is suspected to be due to the overall decrease in immune activity as previously discussed.89 The viral shedding, determined as viral copies/salivary-mL, for three viruses of the family, Herpesviridae: Epstein–Barr virus (EBV), Varicella Zoster Virus (VZV) and Cytomegalovirus (CMV), is known to significantly increase during spaceflight.17 A linear relationship between duration of spaceflight and viral shedding (viral copy numbers) was also identified in the same study. A previous study targeting VZV showcased that saliva samples of the ISS crew contained live, infectious viral particles.90 Increased viral load in oral/respiratory secretions may cause an increased risk of transmission during prolonged spaceflight. All current studies on viral shedding during spaceflight are limited to a 6-month timeframe, due to the nature of spaceflight missions. The effects of prolonged spaceflight to viral shedding beyond the 6 months are, therefore, not documented. Furthermore, adaptive immune system function remains impaired during spaceflight of up to 6 months in duration, which could further contribute to increased viral shedding and an increasing risk of infection.91 A list of DNA viruses with known implications to medical astro-microbiology can be seen in Table 1. As a countermeasure to the above observations, it has been suggested that astronauts would need to be vaccinated against the VZV prior to spaceflight.17 The overall link between microgravity and viral shedding is yet unclear. Increased stress and reduced immunity during spaceflight are also anticipated to play a key role in latent viral reactivation in the ganglion, with saliva shedding to follow.17 Last, it can be hypothesized that viral shedding and transmissibility could be a lesser concern for Martian settlements due to Mars gravity (38% that of Earth’s gravity) mitigating the risk for viral reactivation in addition to reversing the effects of microgravity on adaptive immunityMN9. Further research is required in that regard.
Overall, during human spaceflight there is a significant risk associated with airborne transmission of viruses. This is currently mitigated by NASA’s HSP aimed to reduce risk for contracting infectious disease during space travel through a combination of vaccination and a 14-day pre-flight quarantine. If space travel becomes accessible to more people and space settlements are established, the application of protocols such as the HSP may be very difficult to enforce and hence, up to date vaccinations for space travellers as well as other in-flight Infection Prevention and Control (IPC) protocols such as the availability of in-flight en-suite isolation rooms with negative pressureMN12 could be beneficial for the mitigation of associated transmission risks.92
2.5.2 Bacteria
In contrast with the ISS virome, the ISS bacteriomeMN13 is well documented and relatively well understood. A comprehensive review of bacterial virulence and antibiotic susceptibility has been previously conducted.94 A key consideration relates to bacterial behaviour in space. Certain bacteria have been reported to demonstrate changes associated with an increase in virulence under spaceflight conditions, based on assessments in in-vivo infection models. This change in bacterial virulence could partly be due to the effects of global regulators (GRs). GRs are transcription factors that coordinate responses to environmental stressors by coordinating the expression of thousands of genes.95 Other studies of bacteria have reported a change or a decrease in markers associated with virulence properties.96 Pivotal to the characterisation of the bacterial diversity on board the ISS have been the Microbial Tracking (MT) 1–3 studies.
Initial culture-independent metataxonomic analysis of the ISS filter debris, using 16S rRNA gene amplicon sequencing, revealed an ISS associated bacteriome dominated by the phyla Actinobacteria (69% relative abundance) and Firmicutes (29.63% relative abundance) with the genera Corynebacterium (phylum Actinobacteria—67.3% relative abundance) and Streptococcus (phylum Firmicutes—20.46% relative abundance) dominating the pyrosequences.25 In parallel, culture-dependant analysis in the same study revealed that from the culturable species, those of the genera Bacillus and Staphylococcus were the most isolated. An absence of reads associated with spore-forming species during the use of metataxonomicsMN14 was noted, attributed to the difficulty of extracting DNA from spore-forming species along with a possible association between microgravity and enhanced hardness of bacterial spores.25 Subsequent shotgun metagenomics analysis identified that the ISS surface bacteriome was dominated by species associated with the human skin, mainly those of Staphylococcus. This verified the culture-dependent findings of previous studies.97 In relation to culture independent approaches, most protocols used during DNA extraction can introduce bias which can distort the true abundance of taxa and species based on differences between the taxa such as DNA yield.98 Overall, Staphylococcus epidermidis was the most predominant bacterial species followed by Cutibacterium acnes, another human skin-associated commensal. These species can be associated with opportunistic infection in certain human cohorts with weakened immune system and both are associated with AMR in clinical settings.99,100,101 The overall risk of infection, however, is considered low. Neither of these two species have previously been associated with astronaut infections during spaceflight. A preliminary examination of the ISS resistome reveals that resistance genes associated with macrolide-lincosamide-streptogramin (MLS) antibiotics are the predominant Antimicrobial Resistance Genes (ARGs) identified; a resistance pattern commonly encountered in skin-associated species such as C. acnes.99,102
Amongst all the studies conducted so far, some bacterial species appear to play an enhanced role in the ISS related bacteriome:
2.5.2.1 Bacilllus cereus sensu lato (s.l.)
Spore forming bacteria have always been a concern from a planetary protection context due to their ability to cause human disease while withstanding disinfection protocols and displaying resistance to the harsh environments of space. One of the most abundant spore-forming species aboard the ISS are these of the Bacillus cereus s.l. group. A group of 11 non-toxin-producing Bacillus cereus strains were recently identified from ISS surfaces and extensively studied.103 These strains displayed close genomic relatedness to Bacillus anthracis and are, therefore, grouped to a distinct B. anthracis clade. In addition, these strains characteristically lacked the plasmids (pXO1, pXO2) associated with B. anthracis virulence.
Pathogenetically, key components of virulence in B. cereus and Bacillus thuringiensis were also missing, and overall clinical characteristics of this B. anthracis clade requires further studies. Several strains of Bacillus amyloliquefaciens (n = 9) and B. thuringiensis (n = 10) have also been isolated on consecutive days from surfaces on the ISS.104 Of note, the B. thuringiensis strains have been shown to possess an array of virulence factors associated with enteropathogenicityMN15 (e.g., non-hemolytic enterotoxin) and the siderophore petrobactin associated with virulence in B. anthracis.105,106 Some of the ISS originating B. thuringiensis strains are phenotypically resistant to carbapenems; a type of resistance rarely reported in Bacillus species.107 It is important to mention that non-toxigenic B. anthracis along with most B. cereus s.l. species are ubiquitously present on Earth and are rarely pathogenic. Further studies are required to fully characterize the medical astro-microbiology implications and any possible health risks associated with this genus during spaceflight.
2.5.2.2 Kalamiella piersonii
Kalamiella is a novel genus in the Enterobacterales order that currently consists of a single species, K. piersonii.108 Kalamiella is the first bacterial genus to be identified outside of the terrestrial environment. Culture independent and machine learning analysis revealed K. piersonii to be highly prevalent in the ISS microbiome and dominating the ISS resistomeMN16.109 Several strains of K. piersonii (n = 33) have been isolated from surfaces of the ISS, dating back to 2016, rendering K. piersonii an organism of interest for medical astro-microbiology. Initial analysis predicted K. piersonii as a non-pathogenic species with no human association. Since its first report in 2019, a few clinical cases of K. piersonii have been reported in humans including bacteraemia, meningitis and kidney stones disease amongst others.110,111 Preliminary genomic analysis of this novel species has identified that all strains examined so far exhibit a multidrug resistant (MDR) phenotype and genotype along with a hypervirulence associated (Hv) genotype. The Hv genotype relates to the presence of a 262 Kbp non mobilizable plasmid encoding for the aerobactin gene cluster (iucA-D/iutA) along with the vibriobactin utilisation protein (viuB) and the virulence transcriptional regulator (virB).112 Drug resistance to cephalosporins, quinolones, aminopenicillins, rifampicin, piperacillin and glycopeptides has already been reported.110,111 Resistance to last resort carbapenem, tigecycline and polymyxin antibiotics has not been reported for any of the K. piersonii strains to date. Given the persistence of K. piersonii on board the ISS, its potential to cause a variety of different infections and its MDR status, further investigations are required to clarify the pathogenicity of this novel human pathogen both in terrestrial and spaceflight settings.
2.5.2.3 Klebsiella pneumoniae
K. pneumoniae is a well-characterized human commensal and pathogen, one associated with hypervirulence and acquired AMR to last resort antimicrobial agents. The World Health Organisation (WHO) has categorised carbapenem-resistant K. pneumoniae (CRKP) as a priority 1 (critical) pathogen for the development of new antibiotics.113 CRKP infections have a reported pooled mortality rate of 42.14% vs 21.16% observed for carbapenem-susceptible K. pneumoniae (CSKP) associated bloodstream infections.114 Klebsiella species are known members of the human gut microbiome so their presence on board the ISS is expected. Indeed, several Klebsiella isolates have been identified from ISS surfaces using culture-dependent methods.115 Interestingly, a recent study on the metabolic modelling of the ISS microbiome revealed K. pneumoniae as a having a key role in metabolic interactions between microorganisms.18 In particular, K. pneumoniae appeared to be exceptionally beneficial for the survival of Pantoea species. Of clinical relevance in terms of polymicrobial infectionsMN17, in actual spaceflight conditions K. pneumoniae appears to be antagonistic (parasitic) against filamentous fungi of the genus Aspergillus in agreement with terrestrial observations.116 Given the clinical relevance and apparent metabolic importance of K. pneumoniae in spaceflight conditions, a complete genomic characterisation of the virulence and drug resistance of the identified K. pneumoniae strains would be beneficial, along with an extended effort of mapping its synergistic and antagonistic interactions in terms of the ISS microbiome.
2.5.2.4 Enterobacter bugadensis
E. bugandensis is a recently identified species of Enterobacter. It is associated with cases of sepsis in neonates and immunocompromised patients.117 Multidrug and metal-resistant strains of E. bugandensis (n = 5) have been isolated from the ISS and presented a close genetic resemblance with the clinically isolated strains EB-247 and 153-ECLO.118 All strains appeared resistant to cefazolin, cefoxitin, oxacillin, penicillin, and rifampicin, while a subset were non-susceptible to ciprofloxacin and erythromycin. Erythromycin is not clinically used to treat Enterobacter species infections, whereas ciprofloxacin is an antibiotic that is used for clinical cases of infections caused by Enterobacter. Resistance to penicillin, cefoxitin and cefazolin is intrinsic in Enterobacter species due to the production of the AmpC beta lactamase.119 The multiple antibiotic resistance (MAR) locus was also reported as a main mediator of resistance in these strains. High levels of MDRMN18 in E. bugandensis was recently observed in clinical strains.117 Clinical options for treatment of such infections in space conditions could be challenging with carbapenems being the antibiotic of choice in that instance.117,120 Only ertapenem is currently available as a carbapenem treatment option on board the ISS.
2.5.2.5 Escherichia coli
E. coli is another member of the order Enterobacterales and as well as a characterised human intestinal commensal. Apart from its scientific benefit, it can also be a versatile human pathogen.121E. coli strains that are associated with human pathogenesis are broadly separated between intestinal pathogenic E. coli (IPEC) or extraintestinal pathogenic E. coli (ExPEC). Aside from its pathogen potential, E. coli strains are known to have a great capacity to accumulate ARGs via horizontal gene transfer with MDR (e.g. ST131) and Extended Drug Resistant (XDR) lineages (e.g. ST361) described so far.122,123Given its ubiquitous dissemination and association with AMR, the effects of microgravity on E. coli’s resistance properties have been a focus of NASA’s autonomous E. coli AntiMicrobial Satellite (EcAMSat) mission. The experiment exposed two strains of AMG1 uropathogenic E. coli (UPEC), a wild type (WT) strain and a strain with a deleted rpoS gene (∆rpoS) (stress response regulator) to spaceflight conditions.124 All strains were grown to stationary phase at 37 °C and tested with three different doses of the antibiotic gentamycin. A parallel ground control experiment was also maintained. The findings suggested that the microgravity exposed strains were more susceptible to gentamycin compared to the ground control strains. The spaceflight strains also exhibited a slower metabolism, with the ∆rpoS mutant being 34–37% less metabolically active compared to the WT.125 The EcAMSat study concluded that the rpoS gene and its downstream products might be good therapeutic targets for treating E. coli induced infections in space and on Earth alike. Other studies exposing E. coli strains to different gentamycin concentrations in spaceflight conditions on board the ISS have presented contradicting results. A 2018 study showed that within 49 h of being cultured, a non-pathogenic E. coli strain ATCC-4157, was able to grow to a higher concentration of gentamycin in spaceflight conditions (>175 μg/mL) compared to the Earthly control (75 μg/mL).126 Additionally, 50 stress-response regulated genes were observed to be upregulated in spaceflight conditions, providing further evidence of the importance of stress-response for E. coli’s spaceflight adaptation. Other experiments conducted on ISS utilising the same ATCC-4157 strain verified the ability of the strain to grow to a higher concentration of gentamicin (>175μg/mL) compared to the Earthly control (75μg/mL).127 Overall, as with other Enterobacterales,MN19 a strain-specific response to space conditions is observed for E. coli. As with other Enterobacterales experiments, an overall increase in experimentation with well-characterised clinical strains could aid in elucidating the clinical relevance of these findings. An overview of bacterial species of medical astro-microbiology interest based on our current understanding can be seen in Table 2.
Some of the opportunistic pathogens that have undergone exposure to spaceflight or microgravity simulated conditions have been observed to have enhanced pathogenic properties in in-vivo models though the clinical significance of these findings require further investigation. While virulence was increased while under the influence of spaceflight conditions, any increase that was observed has been noted to decrease to pre-flight levels upon a return to Earth.19
2.5.3 Bacterial Pathogens with Evidence of Enhanced Virulence in Spaceflight Conditions
The most well-documented example of microgravity-associated enhancement of virulence relates to Salmonella enterica SSalmonella enterica serovar Typhimurium S. typhimurium is a zoonotic pathogen that is commonly associated with self-limiting gastroenteritis in humans and occasionally associated with blood stream infections. Enhanced virulence for S. typhimurium has been reported in murine infection modelsMN20 during spaceflight.128,130 The enhanced virulence was identified based on the observation of a reduction in LD50 value and an increase in both percent mortality and time to death from point of infection for mice infected with spaceflight associated cultures compared to ground control cultures. This enhanced virulence was likely regulated by the environmental response regulatorMN21 RNA-binding protein Hfq.128 These findings were further supported by a study conducted on Salmonella enterica Serovar Enteritidis during spaceflight (1 month duration). The study revealed that spaceflight was associated with an enhanced growth rate compared to the ground control. Differentially expressed proteins associated with energy production and transmembrane transport were also reported.131 Furthermore, the same study identified that the microgravity induced downregulation of the oppA gene, a member of the oligopeptide transport system OPP, leading to amikacin resistance. The opportunistic pathogen Serratia marcescens was also shown to undergo spaceflight-induced changes associated with enhanced virulence as this was evaluated in a Drosophila melanogaster infection model. The reported virulence associated changes were proposed to be microgravity associated.19 S. marcescens is a pathogen with increasing rates of drug resistance amongst clinical isolates and is commonly associated with nosocomial infections including bacteraemia.132 The Gram-positive skin commensal Staphylococcus warneri was also observed to rapidly adapt to microgravity and radiation conditions during prolonged spaceflight (79 days duration). Notable changes included an increase in its biofilm formation ability, while subtle changes to the genome (15 InDels) and phenome (cell wall hardness and chemical sensitivity) were also observed.133 S. warneri as most other coagulase-negative staphylococci is rarely associated with infections in healthy individuals and is mostly associated with infection (e.g. bacteraemia) in individuals with prosthetic devices.134,135
Selective pressure imposed by microgravity exposure is currently hypothesised to be the predominant causative agent for the observed enhancement of pathogenic properties in some bacterial species. Microgravity has been shown to have influence on microbial properties including enhancing stress resistance of bacteria.136 The exact mechanism behind these effects is currently not known. Due to the difficulty of conducting experiments in spaceflight conditions, terrestrial simulated microgravity models are often utilised, in specific low shear modelled microgravity (LSMMG)MN22 simulations.
However, not all pathogens undergo an enhancement of virulence when exposed to microgravity conditions.
2.5.4 Bacterial Pathogens with Evidence of Reduced Virulence in Spaceflight Conditions
Methicillin-resistant Staphylococcus aureus (MRSA), Listeria monocytogenes and Enterococcus faecalis are all pathogens that have been observed to have a reduction in virulence on Earth based spaceflight analog models.137 A thorough study focused on the in-vivo virulence of Klebsiella pneumoniae, Pseudomonas aeruginosa and Proteus mirabilis strains in larval and adult worm models under spaceflight conditions. Overall, spaceflight appeared to reduce the virulence of Klebsiella pneumoniae strain ATCC-8052, whereas the virulence of Proteus mirabilis strain ATCC-4630 and Pseudomonas aeruginosa strain ATCC-BAA-47 remained unaffected.138 Acinetobacter baumanii and Acinetobacter schindleri are human opportunistic pathogens often associated with Hospital Acquired Infections (HAIs) and have both been shown to have decreased biofilm formation abilities after spaceflight on the Shenzoun 10 and 11 spacecrafts commissioned by China National Space Administration (CNSA).139,140 To confirm these findigs, coherent international effors are required. Experiments in LSMMG conditions for Yersinia pestis (the causative agent of bubonic, septicaemic, and pneumonic plague) also reported a decreased virulence potential as this was evaluated in cell culture infection assays.141 For most of these experiments, strains from the American Tissue Type Collection (ATCC)MN23 were selected. Future experiments could utilise clinical strains with a demonstrated hypervirulence phenotype and genotype such as strains of Hypervirulent K. pneumoniae (hvKp). Documenting the effects of microgravity and radiation (UV, ionising) on hypervirulent strains would clarify the clinical significance of the reported reduced virulence findings. A summary of bacterial and fungal pathogens with evidence of increased virulence during spaceflight can be seen in Fig. 2.
2.5.5 Antimicrobial Resistance (AMR)
Overall, AMR can be seen as an ecological consequence of the widespread use of antibiotics. Antibiotic-resistant organisms (AROs) are frequently encountered in healthcare settings where antibiotic selective pressure is intensive. AMR is often referred to as a ‘silent pandemic’. The effects of spaceflight conditions on AMR appears to be species and even strain specific, although it is evident that most species very rapidly adapt to antibiotic exposure in simulated microgravity conditions using LSMMG apparatus. Further studies could clarify if AMR associated adaptability is different in actual microgravity conditions and Earth. In contrast with Earth, treatment options during spaceflight are very limited and medical interventions are vastly more complicated.94 Taking this into account, antibiotic usage and AMR dissemination in spaceflight needs to be closely monitored.
Isolates of Enterobacter found on ISS surfaces have been identified to possess the metallo-beta-lactamase encoding IMP-2 gene that is known to confer resistance to carbapenems, clinically last resort antibiotics reserved for treatment of complicated infections.142 Phenotypic resistant to carbapenems (ertapenem and meropenem) for ISS originating strains of Bacillus has also recently been identified, with current efforts focussing on elucidating whether its intrinsic or acquired (ongoing research). E. coli has also been shown to rapidly adapt to LSMMG conditions with emerging resistance to cefalotin, cefuroxime, cefuroxime axetil, cefoxitin, and tetracycline after 1000 bacterial generations.143 The isogenic strains of this experiment were grown in high-aspect-ratio vessels (HARVs) intermittently exposed to chloramphenicol between cycles to prevent contamination of the samples. Resistance in E. coli appeared to be caused by a combination of increased mutagenesis along with three transposon mediated rearrangements. The same study when repeated with the intermittent use of steam for sterilization instead of chloramphenicol did not result in acquired antibiotic resistance.144 Overall, the findings of these studies suggest that simulated microgravity conditions do not appear to reduce the antibiotic stress adaptation for the tested E. coli strains.
The most common method of dissemination of antimicrobial resistance genes (ARGs) is through mobile genetic elements (MGEs).MN24 The ISS and the Antarctic Research Station Concordia (ARSC) are both confined and secluded built environments that experience extreme conditions with the ARSC being used as a model environment for space travel.145 The major difference between the two habitats is the inclusion of radiation and microgravity as environmental pressures aboard the ISS. A study has been conducted comparing AMR and the conjugative transfer capacity of Staphylococcus and Enterococcus isolates on the ISS and in the ARSC. In this study, the ISS strains showed a higher abundance of ARG carriage, compared to the ARSC strains.146 Interestingly, the ISS strains were also shown to possess higher horizontal gene transfer (HGT)MN25 capacity via the presence of virulence regulatory genes (vir). Virulence regulatory genes have been extensively identified in the accessory genome of ISS strains and could be tested as markers for microgravity induced virulence.
Studies using culture independent methods looking at ISS surfaces have revealed a complex ISS resistome, with more than 123 ARGs identified, with those for β-lactam and trimethoprim resistance identified as the most prevalent.142 HGT abilities measured in both the ISS and in the LSMMG scenarios on Earth have revealed species dependant changes, with the Bacillus species possibly showcasing an increased plasmid transfer efficiency.147 Apart from Bacillus species the overall HGT rate for other Gram-negative bacteria tested in microgravity conditions remained unaffected.148,149 A recent study using S. aureus strains clearly demonstrated that simulated microgravity directly promotes HGT of ARGs even in the absence of antibiotic selective pressure.150 The overall pattern seen for AMR and HGT under the influence of microgravity is the same as that seen for virulence: highly variable and species specific. Overall, it is evident that a one-fits-all approach is not adequate to map the effects of microgravity and overall spaceflight on AMR and the dissemination of ARGs. Therefore, a coordinated effort is required to understand, document and map these effects in more clinically relevant species and strains.
2.5.6 Fungi
Similar to the absence of a universal effect of spaceflight-related environmental factors on the pathogenic properties of bacteria, there is no universal positive or negative effect of spaceflight on fungi. Overall, filamentous fungi appear well adapted to spaceflight conditions. Metataxonomic analysis of ISS surfaces utilising the fungal Internal Transcribed Spacer (ITS) region, revealed a fungal population comprised of one phylum and eleven genera151 The culture-dependent methods employed by the same study identified 81 cultivatable fungal isolates which were dominated by Rhodotorula mucilaginosa (41% of the isolates) and Penicillium chrysogenum (15% of the isolates).
Analysis conducted for two Aspergillus fumigatus strains isolated from air and surfaces of the ISS identified that the ISS strains exhibited enhanced lethality in a neutrophil-deficient larval zebrafish model of invasive aspergillosis compared to clinical isolates (Af293 and CEA10).152,153 Aspergillus fumigatus has also been isolated from HEPA filters aboard the ISS as part of the Microbial Observatory Experiments. ISS A. fumigatus strains presented an increased abundance of proteins associated with stress responses (Pst2, ArtA) and carbohydrate and secondary metabolism (PdcA, AcuE).26 An increase in toxin production (Asp-hemolysin) was also reported in the same study, hinting to a potential increase in virulence. Indeed, a follow-up analysis on ISS A. fumigatus strains utilising larval zebrafish virulence assays reported a strain-specific increase in secondary metabolites (SMs) related to radiation (UV-C) protection and enhanced virulence.154 The human commensal and opportunistic pathogen Candida albicans was also shown to exhibit an increase in both virulence and resistance against the antifungal agent amphotericin-B during spaceflight conditions.155 A study conducted on the ChangZheng 5 space shuttle on the entomopathogenic fungus, Beauveria bassiana, revealed a series of SMs (toxins) produced exclusively by the spaceflight associated strains, with an overall insecticidal activity.138,156 As part of the “Veggie” project (an ISS based project for studying the effect of plant growth and function in spaceflight conditions), the Zinnia hybrida plants utilised in the study became infected with the widespread plant and opportunistic human fungal pathogen Fusarium oxysporum.157 Two F. oxysporum isolates were recovered from the infected plants and genomic analysis revealed a close genetic relatedness with strains isolated following the Chernobyl disaster as well as a clinical strain (FOSC 3-a) from a blood culture of a patient with fusariosis. F. oxysporum strains have also been isolated from the dining table of the ISS.158 These strains were studied in a context of a virulence assay using an immunocompromised Caenorhabditis elegans model of fusariosisMN26. Both strains appeared capable of establishing an infection, with one strain (ISS-F40) showing enhanced virulence abilities via hypha piercing and other mechanisms.
Aspergillus nidulans strains have also been characterised for genomic, proteomic and metabolomic changes under spaceflight conditions.159 The ISS grown A. nidulans samples showed positive selectionMN27 for a small subset of protein coding genes (n = 5). Interestingly, genomic indications of variations in transposable element activity were also noted under spaceflight conditions as reported for the bacteria of the species S. aureus.160 Overall, through heterogeneous genomic expression, A. nidulans has been proposed as a host capable for the production of secondary metabolites with antibiotic activity during prolonged spaceflight in deep space, which can be used in case spacecraft therapeutic stocks are exhausted. Another species of Aspergillus that has been isolated and studied from on board the ISS is that of Aspergillus niger. A. niger is a ubiquitous fungus that thrives in environments like the ISS. Initial metabolomic based analyses of the A. niger ISS isolated strain JSC-093350089 reported an increased production of naphtho-γ-pyrone along with potentially therapeutically relevant secondary metabolites including the antioxidant pyranonigrin A.154,161 Subsequent experiments comparing the same A. niger exposed to the ISS conditions against a ground control revealed that ISS conditions permanently altered the strains metabolic functions with a significant enhancement in production of the pyranonigrin A.162 A summary of fungal pathogens with medical astro-microbiology association can be seen in Table 3.
2.6 Global Public Health and the Global Environment
It is evident that specific bacterial and fungal species adapt and change as an effect of spaceflight conditions. So far, our understanding of the risks (if any) of re-introducing these spaceflight adapted microorganisms back to Earth is very limited. Although several new bacterial species and one bacterial genus have been described on ISS,129,164 there were very likely originating from the crew’s own microbiome and cargo-associated contamination. Re-introduction of spaceflight changed microorganisms back to Earth could pose the risk (however small) of a microbiological invasion with environmental and public health consequences. Microbial invasion in established ecosystems is a topic not currently very well understood.165 As with invasive plants and animals, the effects of invasive microbes to the composition and functioning of ecosystems is significant.165 It has been suggested that invasion consists of four main stages including (i) the transport of invasive species outside of their native environment, (ii) the introduction of invasive species into the new environment, (iii) the establishment of the invasive species, and (iv) the spread of invasive species and subsequent impact on the ecosystem165 (Fig. 3). These invasive microorganisms could be pathogenic or non-pathogenic and could be introduced accidentally or purposely. There are several specific examples of such microbial invasions. One includes the invasion of the fungus Fusarium circinatum, a key pathogen of Pinus species.MN28 This plant pathogen was disseminated globally by insect vectors and the wind causing severe pine infections that altered the pine forest composition to oak-dominated woodlands.166 Another example includes a north America native racoon species (Procyon lotor) which introduced to Europe the nematode Baylisascaris procyonis, a parasite that in rare events can cause severe neurologic and ocular disease in humans.167 Overall, in the last centuries over 16,000 invasive species introductions have been recorded globally.168 In terms of association of invasive microbial species with human health; invasive mirobial specis can either act as a source of new pathogens or amplify other local pathogens.169 Microbial species discussed in this review showing high adaptability in spaceflight conditions would be more likely to act as invasive species upon their putative re-introduction to the terrestrial environment. Their putative re-introduction could either occur via crew colonisation during spaceflight or via cargo contamination prior to returning to Earth. A co-ordinated research effort is required to survey strains from microbial species with increased spaceflight adaptability and mitigate the risk (however small) of a spaceflight associated microbial invasive species introduction event.
3 Celestial Body Habitation
In addition to spaceflight, a different set of considerations relates to the permanent presence of humans on the surface of other celestial bodies. Within the next few decades this is expected to be true for Mars and the Moon. Proposals for human presence on other planets including Venus, or even Jovian moons (e.g., Callisto) are in place, though such human presence is unlikely within the twenty-first century timeframe.170 Possible signs of microbial life have also recently been reported on one of Saturn’s moon Enceladus, in terms of geochemical processes alone being unable to explain the levels of methane measured by the Cassini spacecraft.171 The environmental conditions on each of these planets and moons is unique and, therefore, different selective pressures would exist on each one. For the purposes of this review, we will focus on Mars as the most relevant for a permanent human presence in the immediate future. The environmental conditions of the Moon have always been hostile to life, and it is accepted that the Moon would be a highly unlikely place for native microbial life. A review on lunar astrobiology has been previously conducted.172,173
On Earth, several Mars Simulation Chambers (MSC)MN29 have been developed to simulate the environmental conditions that will be encountered by the first Mars settlements.174 MSCs are stainless steel low-pressure cylindrical chambers which simulate the following five environmental components of Mars’s surface: (i) pressure, (ii) UV radiation, (iii) dust loading, (iv) temperature, and (v) atmospheric gas mixture.175 One study used an MSC approach to evaluate the survival on Mars of E. coli as a key potential spacecraft contaminant. The main findings related to the ability of E. coli cells to survive on Mars soil conditions over a period of 7 days; however, they were not able to replicate. Desiccation (0.71 kPa) was identified as the key limiting factor for the resurrection of viable cells on Mars simulated soil.176 The effect on the mycobiome due to human presence in Moon/Mars analogue habitats over a 30-day period has also been investigated.177 Human presence appeared to significantly impact fungal diversity with the fungal genera of Epicoccum, Alternaria, Pleosporales, Davidiella and Cryptococcus, presenting an increased abundance. These fungal genera are established plant pathogens and human opportunistic pathogens; hence additional studies are required to evaluate their health impact to plants and human is such sealed habitats.178,179,180,181 A thorough analysis on filamentous fungi from the ISS and from Chernobyl exposed to simulated Mars conditions (SMCs) has also been conducted.26 As with previous studies conducted on ISS fungal strains, adaptation to SMCs appeared to occur via alterations of SM production, such as starvation response enzymes. Overall, adaptation to SMCs, as with spaceflight conditions, appears to be species specific for fungi. Like microgravity simulations on Earth, it is not currently possible to exactly replicate the stressors encountered on Mars. Hence, the exact impact of the Martian environmental stressors could be better verified with on-site autonomous or human experiments.
Native microbial life on Mars, although not yet identified is perceived as possible given the Earth like conditions in Mars 3.8 billion years ago.182 Robotic exploration to date has purposely avoided the exploration of potential “Special Regions”,MN30 places on the planet with high chance of being inhabited by extant Martian life.23 The main reason relates to forward Planetary Protection policies, aimed at protecting Mars with microbial contamination originating from Earth138. Given the radiation dosage reaching the surface of Mars, microbial life if it has survived, is likely to be buried below the surface. Simulating ionising radiation conditions encountered on Mars, a recent study estimated that the extremophilic Deinococcus radiodurans could survive over 100 million years buried 10 m below Mars’s surface.183 This finding was quantified using cell manganese antioxidant accumulation as a sign of tolerance to different forms of radiation. This raises the possibility that if microbial life ever existed on Mars, it could still be possibly viable with unchartered potential effects and interactions with Earth’s biosphere. There is the possibility, therefore, however small, that the first Mars explorers could be exposed to Mars native microbial life. To mitigate any risk of accidental exposure, facilities similar to Biosafety Level 4 (BSL-4) laboratories used for studying highly pathogenic viruses on Earth, should be pre-planned and become immediately accessible before any microbial identification experiments take place by human personnel. An understanding of how pathogens adapt and behave in Martian environmental conditions is also required prior to human settlement to mitigate any public health risks to the first human settlements.
4 Conclusion
The future path of humanity appears to progressively expand beyond the terrestrial environment. Managing the microbiological and infectious risks and associated fears arising from this are key to safety, sustainability, and public and overall government support for this endeavour. As outlined, we currently have very limited understanding of many of the risks in relation to the microbiome, the factors that drive its adaptation and of the host factors that contribute to susceptibility to colonisation and infection. In relation to causality for changes in microorganisms and hosts associated with space travel, attention has naturally focused on microgravity and radiation exposure but as outlined throughout this review there are many other factors that may be as important or more important in shaping the microbiome of the space vehicle and the response of the host to that environment. Review and reflection on the current literature in the framework of the risks and variables points to several conclusions.
There are extensive gaps in our understanding of how space travel reshapes terrestrial microorganisms and impacts on host resistance to infection. Human space travel introduces terrestrial organisms into space environments and organisms from space environments back into terrestrial environments. This exchange will increase along with an increased human presence in space. In that context, surveillance of space environments and of infection or other microbial impacts associated with space travel is important. The risk of introducing a harmful microorganism that has adapted within a spacecraft environment and is capable of dissemination in the terrestrial environment is very low but requires caution and surveillance regardless.
The interior of a spacecraft will inevitably develop a microbiome that will adapt over time to that environment. Protocols that attempt to maintain low-biomass of the spacecraft environment are likely to drive that adaptation towards a unique closed habitat that is tolerant of the disinfectants and the antimicrobial coating of surfaces used to maintain a clean room type environment. Processes more like those that apply in a clean domestic setting may lead to a more terrestrial like microbiome mitigating the effects of ultra-clean environments to human health. A balance between a more ‘natural’ spaceflight environment and planetary protection from human contamination can be managed and achieved.
Human travel to other celestial bodies will inevitably lead to introduction of microorganisms to those environments. Local containment will likely be very challenging if the environment can support growth of terrestrial microbes. How terrestrial microorganisms will adapt and change in these extra-terrestrial environments is not currently understood. Furthermore, there is the risk, however small, that human settlers might encounter extra-terrestrial microbial life. Celestial body habitation requires thorough planning, containment and mitigation strategies from a medical astro-microbiology perspective. Overall, a framework carefully built around the microbiological and infectious disease considerations would ensure the long-term viability of our multi-planetary aspirations.
References
Piret J, Boivin G (2021) Pandemics throughout history. Front Microbiol. https://doi.org/10.3389/fmicb.2020.631736
Baker RE, Mahmud AS, Miller IF, Rajeev M, Rasambainarivo F, Rice BL, Takahashi S, Tatem AJ, Wagner CE, Wang L-F, Wesolowski A, Metcalf CJE (2022) Infectious disease in an era of global change. Nat Rev Microbiol 20:193–205
Ellwanger JH, de Kaminski VL, Chies JAB (2019) Emerging infectious disease prevention: where should we invest our resources and efforts? J Infect Public Health 12:313–316
Yu D, Li X, Yu J, Shi X, Liu P, Tian P (2021) Whether urbanization has intensified the spread of infectious diseases—renewed question by the COVID-19 pandemic. Front Public Health. https://doi.org/10.3389/fpubh.2021.699710
Carlson CJ, Albery GF, Merow C, Trisos CH, Zipfel CM, Eskew EA, Olival KJ, Ross N, Bansal S (2022) Climate change increases cross-species viral transmission risk. Nature 607:555–562
Nordmann P, Poirel L (2019) Epidemiology and diagnostics of carbapenem resistance in gram-negative bacteria. Clin Infect Dis 69:S521–S528
Simon V, Ho DD, Abdool Karim Q (2006) HIV/AIDS epidemiology, pathogenesis, prevention, and treatment. Lancet 368:489–504
Bunge EM, Hoet B, Chen L, Lienert F, Weidenthaler H, Baer LR, Steffen R (2022) The changing epidemiology of human monkeypox—a potential threat? A systematic review. PLoS Negl Trop Dis 16:e0010141
Lytras T, Tsiodras S (2021) Lockdowns and the COVID-19 pandemic: what is the endgame? Scand J Public Health 49:37–40
Early R, Bradley BA, Dukes JS, Lawler JJ, Olden JD, Blumenthal DM, Gonzalez P, Grosholz ED, Ibañez I, Miller LP, Sorte CJB, Tatem AJ (2016) Global threats from invasive alien species in the twenty-first century and national response capacities. Nat Commun 7:12485
de Castro MCT, Fileman TW, Hall-Spencer JM (2017) Invasive species in the Northeastern and Southwestern Atlantic Ocean: a review. Mar Pollut Bull 116:41–47
Shimura J, Coates D, Mulongoy JK (2010) The role of international organisations in controlling invasive species and preserving biodiversity. Rev Sci Techn l’OIE 29:405–410
Wallenborn JT, Vonaesch P (2022) Intestinal microbiota research from a global perspective. Gastroenterol Rep (Oxf). https://doi.org/10.1093/gastro/goac010
Johnson LB, Davis JR, Polk JD, Whitson P, Jett B (2010) Flight crew health stabilization program. https://ntrs.nasa.gov/api/citations/20130000048/downloads/20130000048.pdf. Accessed 8 Dec 2022
NASA (2020) NASA’s plan for sustained lunar exploration and development. https://www.nasa.gov/sites/default/files/atoms/files/a_sustained_lunar_presence_nspc_report4220final.pdf. Accessed 15 Dec 2022
NASA (2022) Moon to Mars objectives. https://go.nasa.gov/3BUkHGL. Accessed 15 Dec 2022
Mehta SK, Laudenslager ML, Stowe RP, Crucian BE, Feiveson AH, Sams CF, Pierson DL (2017) Latent virus reactivation in astronauts on the international space station. NPJ Microgravity 3:11
Kumar RK, Singh NK, Balakrishnan S, Parker CW, Raman K, Venkateswaran K (2022) Metabolic modeling of the International Space Station microbiome reveals key microbial interactions. Microbiome 10:102
Gilbert R, Torres M, Clemens R, Hateley S, Hosamani R, Wade W, Bhattacharya S (2020) Spaceflight and simulated microgravity conditions increase virulence of Serratia marcescens in the Drosophila melanogaster infection model. NPJ Microgravity 6:4
Hallsworth JE (2021) Mars’ surface is not universally biocidal. Environ Microbiol 23:3345–3350
Simões MF, Antunes A (2021) Microbial pathogenicity in space. Pathogens 10:450
Warmflash D, Larios-Sanz M, Jones J, Fox GE, McKay DS (2007) Biohazard potential of putative Martian organisms during missions to Mars. Aviat Space Environ Med 78:A79-88
Rummel JD, Beaty DW, Jones MA, Bakermans C, Barlow NG, Boston PJ, Chevrier VF, Clark BC, de Vera J-PP, Gough RV, Hallsworth JE, Head JW, Hipkin VJ, Kieft TL, McEwen AS, Mellon MT, Mikucki JA, Nicholson WL, Omelon CR, Peterson R, Roden EE, Sherwood Lollar B, Tanaka KL, Viola D, Wray JJ (2014) A new analysis of Mars “special regions”: findings of the second MEPAG special regions science analysis group (SR-SAG2). Astrobiology 14:887–968
Kuehnast T, Abbott C, Pausan MR, Pearce DA, Moissl-Eichinger C, Mahnert A (2022) The crewed journey to Mars and its implications for the human microbiome. Microbiome 10:26
Venkateswaran K, Vaishampayan P, Cisneros J, Pierson DL, Rogers SO, Perry J (2014) International Space Station environmental microbiome—microbial inventories of ISS filter debris. Appl Microbiol Biotechnol 98:6453–6466
Blachowicz A, Chiang AJ, Elsaesser A, Kalkum M, Ehrenfreund P, Stajich JE, Torok T, Wang CCC, Venkateswaran K (2019) Proteomic and metabolomic characteristics of extremophilic fungi under simulated Mars conditions. Front Microbiol. https://doi.org/10.3389/fmicb.2019.01013
Ferranti F, del Bianco M, Pacelli C (2020) Advantages and limitations of current microgravity platforms for space biology research. Appl Sci 11:68
Turroni S, Magnani M, Pukar KC, Lesnik P, Vidal H, Heer M (2020) Gut microbiome and space travelers’ health: state of the art and possible pro/prebiotic strategies for long-term space missions. Front Physiol. https://doi.org/10.3389/fphys.2020.553929
Tesei D, Jewczynko A, Lynch A, Urbaniak C (2022) Understanding the complexities and changes of the astronaut microbiome for successful long-duration space missions. Life 12:495
Guo J-H, Qu W-M, Chen S-G, Chen X-P, Lv K, Huang Z-L, Wu Y-L (2014) Keeping the right time in space: importance of circadian clock and sleep for physiology and performance of astronauts. Mil Med Res 1:23
Pirofski L, Casadevall A (2002) The meaning of microbial exposure, infection, colonisation, and disease in clinical practice. Lancet Infect Dis 2:628–635
Alverdy JC, Luo JN (2017) The influence of host stress on the mechanism of infection: lost microbiomes, emergent pathobiomes, and the role of interkingdom signaling. Front Microbiol 8:322. https://doi.org/10.3389/fmicb.2017.00322. PMID: 28303126; PMCID: PMC5332386
Morrison MD, Thissen JB, Karouia F, Mehta S, Urbaniak C, Venkateswaran K, Smith DJ, Jaing C (2021) Investigation of spaceflight induced changes to astronaut microbiomes. Front Microbiol. https://doi.org/10.3389/fmicb.2021.659179
Hodkinson PD, Anderton RA, Posselt BN, Fong KJ (2017) An overview of space medicine. Br J Anaesth 119:i143–i153
Gundel A, Drescher J, Spatenko Y, Polyakov V (2002) Changes in basal heart rate in spaceflights up to 438 days. Aviat Space Environ Med 73:17–21
NASA (2011) NASA FAQ: astronauts answer student questions. www.jsc.nasa.gov/sightings/index.html. Accessed 15 Dec 2022
SpaceX (2022) The Moon. https://www.spacex.com/human-spaceflight/moon/. Accessed 8 Dec 2022
SpaceX (2020) Mars & beyond. https://www.spacex.com/human-spaceflight/mars/. Accessed 8 Dec 2022
Sonnenfeld G (2005) The immune system in space, including earth-based benefits of space- based research. Curr Pharm Biotechnol 6:343–349
Juhl OJ, Buettmann EG, Friedman MA, DeNapoli RC, Hoppock GA, Donahue HJ (2021) Update on the effects of microgravity on the musculoskeletal system. NPJ Microgravity 7:28
Smith SM, Zwart SR, Douglas GL, Heer M (2014) Human adaptation to spaceflight: the role of food and nutrition. Government Printing Office, NASA
Crucian BE, Choukèr A, Simpson RJ, Mehta S, Marshall G, Smith SM, Zwart SR, Heer M, Ponomarev S, Whitmire A, Frippiat JP, Douglas GL, Lorenzi H, Buchheim J-I, Makedonas G, Ginsburg GS, Ott CM, Pierson DL, Krieger SS, Baecker N, Sams C (2018) Immune system dysregulation during spaceflight: potential countermeasures for deep space exploration missions. Front Immunol. https://doi.org/10.3389/fimmu.2018.01437
Akiyama T, Horie K, Hinoi E, Hiraiwa M, Kato A, Maekawa Y, Takahashi A, Furukawa S (2020) How does spaceflight affect the acquired immune system? NPJ Microgravity 6:14
Crucian B, Babiak-Vazquez A, Johnston S, Pierson D, Ott CM, Sams C (2016) Incidence of clinical symptoms during long-duration orbital spaceflight. Int J Gen Med 9:383–391
Guéguinou N, Huin-Schohn C, Bascove M, Bueb J-L, Tschirhart E, Legrand-Frossi C, Frippiat J-P (2009) Could spaceflight-associated immune system weakening preclude the expansion of human presence beyond Earth’s orbit? J Leukoc Biol 86:1027–1038
Wotring VE (2015) Medication use by U.S. crewmembers on the International Space Station. FASEB J 29:4417–4423
Mehta SK, Crucian BE, Stowe RP, Simpson RJ, Ott CM, Sams CF, Pierson DL (2013) Reactivation of latent viruses is associated with increased plasma cytokines in astronauts. Cytokine 61:205–209
Rooney BV, Crucian BE, Pierson DL, Laudenslager ML, Mehta SK (2019) Herpes virus reactivation in astronauts during spaceflight and its application on earth. Front Microbiol. https://doi.org/10.3389/fmicb.2019.00016
Gilbert JA, Blaser MJ, Caporaso JG, Jansson JK, Lynch SV, Knight R (2018) Current understanding of the human microbiome. Nat Med 24:392–400
Avila-Herrera A, Thissen J, Urbaniak C, Be NA, Smith DJ, Karouia F, Mehta S, Venkateswaran K, Jaing C (2020) Crewmember microbiome may influence microbial composition of ISS habitable surfaces. PLoS ONE 15:e0231838
Mora M, Mahnert A, Koskinen K, Pausan MR, Oberauner-Wappis L, Krause R, Perras AK, Gorkiewicz G, Berg G, Moissl-Eichinger C (2016) Microorganisms in confined habitats: microbial monitoring and control of intensive care units, operating rooms, cleanrooms and the International Space Station. Front Microbiol 7:1573
Fernandes A, Oliveira A, Soares R, Barata P (2021) The effects of ionizing radiation on gut microbiota, a systematic review. Nutrients 13:3025
Siddiqui R, Qaisar R, Goswami N, Khan NA, Elmoselhi A (2021) Effect of microgravity environment on gut microbiome and angiogenesis. Life 11:1008
Mora M, Wink L, Kögler I, Mahnert A, Rettberg P, Schwendner P, Demets R, Cockell C, Alekhova T, Klingl A, Krause R, Zolotariof A, Alexandrova A, Moissl-Eichinger C (2019) Space Station conditions are selective but do not alter microbial characteristics relevant to human health. Nat Commun 10:3990
Kampf G (2018) Biocidal agents used for disinfection can enhance antibiotic resistance in gram-negative species. Antibiotics 7:110
Fahimipour AK, Benmaamar S, McFarland AG, Blaustein RA, Chen J, Glawe AJ, Kline J, Green JL, Halden RU, van den Wymelenberg K, Huttenhower C, Hartmann EM (2018) Antimicrobial chemicals associate with microbial function and antibiotic resistance indoors. mSystems. https://doi.org/10.1128/mSystems.00200-18
Ahn J, Hayes RB (2021) Environmental influences on the human microbiome and implications for noncommunicable disease. Annu Rev Public Health 42:277–292
Wingfield B, Lapsley C, McDowell A, Miliotis G, McLafferty M, O’Neill SM, Coleman S, McGinnity TM, Bjourson AJ, Murray EK (2021) Variations in the oral microbiome are associated with depression in young adults. Sci Rep 11:15009
DeGruttola AK, Low D, Mizoguchi A, Mizoguchi E (2016) Current understanding of dysbiosis in disease in human and animal models. Inflamm Bowel Dis 22:1137–1150
Korf JM, Ganesh BP, McCullough LD (2022) Gut dysbiosis and age-related neurological diseases in females. Neurobiol Dis 168:105695
Gupta A, Bhanushali S, Sanap A, Shekatkar M, Kharat A, Raut C, Bhonde R, Shouche Y, Kheur S, Sharma A (2022) Oral dysbiosis and its linkage with SARS-CoV-2 infection. Microbiol Res 261:127055
Bernard-Raichon L, Venzon M, Klein J, Axelrad JE, Zhang C, Sullivan AP, Hussey GA, Casanovas-Massana A, Noval MG, Valero-Jimenez AM, Gago J, Putzel G, Pironti A, Wilder E, Obaid A, Lu-Culligan A, Nelson A, Brito A, Nunez A, Martin A, Watkins A, Geng B, Kalinich C, Harden C, Todeasa C, Jensen C, Kim D, McDonald D, Shepard D, Courchaine E, White EB, Song E, Silva E, Kudo E, DeIuliis G, Rahming H, Park H-J, Matos I, Nouws J, Valdez J, Fauver J, Lim J, Rose K-A, Anastasio K, Brower K, Glick L, Sharma L, Sewanan L, Knaggs L, Minasyan M, Batsu M, Petrone M, Kuang M, Nakahata M, Campbell M, Linehan M, Askenase MH, Simonov M, Smolgovsky M, Sonnert N, Naushad N, Vijayakumar P, Martinello R, Datta R, Handoko R, Bermejo S, Prophet S, Bickerton S, Velazquez S, Alpert T, Rice T, Khoury-Hanold W, Peng X, Yang Y, Cao Y, Strong Y, Thorpe LE, Littman DR, Dittmann M, Stapleford KA, Shopsin B, Torres VJ, Ko AI, Iwasaki A, Cadwell K, Schluter J (2022) Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia. Nat Commun 13:5926
Arya NR, Rafiq NB (2022) Candidiasis. StatPearls Publishing, Treasure Island (FL)
Navaneethan U (2010) Clostridium difficile infection and inflammatory bowel disease: understanding the evolving relationship. World J Gastroenterol 16:4892
Lobionda S, Sittipo P, Kwon HY, Lee YK (2019) The role of gut microbiota in intestinal inflammation with respect to diet and extrinsic stressors. Microorganisms 7:271
Caio G, Lungaro L, Segata N, Guarino M, Zoli G, Volta U, de Giorgio R (2020) Effect of gluten-free diet on gut microbiota composition in patients with celiac disease and non-celiac gluten/wheat sensitivity. Nutrients 12:1832
Li P, Shi J, Zhang P, Wang K, Li J, Liu H, Zhou Y, Xu X, Hao J, Sun X, Pang X, Li Y, Wu H, Chen X, Ge Q (2015) Simulated microgravity disrupts intestinal homeostasis and increases colitis susceptibility. FASEB J 29:3263–3273
Jiang P, Green SJ, Chlipala GE, Turek FW, Vitaterna MH (2019) Reproducible changes in the gut microbiome suggest a shift in microbial and host metabolism during spaceflight. Microbiome 7:113
Voorhies AA, Mark Ott C, Mehta S, Pierson DL, Crucian BE, Feiveson A, Oubre CM, Torralba M, Moncera K, Zhang Y, Zurek E, Lorenzi HA (2019) Study of the impact of long-duration space missions at the International Space Station on the astronaut microbiome. Sci Rep 9:9911
Ratcliffe MJH (2016) Encyclopedia of immunobiology. Academic Press, Amsterdam
Ege MJ (2017) The hygiene hypothesis in the age of the microbiome. Ann Am Thorac Soc 14:S348–S353
Jhun I, Phipatanakul W (2016) Early exposure to dogs and farm animals reduces risk of childhood asthma. Evid Based Med 21:80–80
Genuneit J (2012) Exposure to farming environments in childhood and asthma and wheeze in rural populations: a systematic review with meta-analysis. Pediatr Allergy Immunol 23:509–518
Tang H, Rising HH, Majji M, Brown RD (2021) Long-term space nutrition: a scoping review. Nutrients 14:194
Bloomfield SF, Stanwell-Smith R, Crevel RWR, Pickup J (2006) Too clean, or not too clean: the hygiene hypothesis and home hygiene. Clin Exp Allergy 36:402–425
Pavletić B, Runzheimer K, Siems K, Koch S, Cortesão M, Ramos-Nascimento A, Moeller R (2022) Spaceflight virology: what do we know about viral threats in the spaceflight environment? Astrobiology 22:210–224
Garrett-Bakelman FE, Darshi M, Green SJ, Gur RC, Lin L, Macias BR, McKenna MJ, Meydan C, Mishra T, Nasrini J, Piening BD, Rizzardi LF, Sharma K, Siamwala JH, Taylor L, Vitaterna MH, Afkarian M, Afshinnekoo E, Ahadi S, Ambati A, Arya M, Bezdan D, Callahan CM, Chen S, Choi AMK, Chlipala GE, Contrepois K, Covington M, Crucian BE, de Vivo I, Dinges DF, Ebert DJ, Feinberg JI, Gandara JA, George KA, Goutsias J, Grills GS, Hargens AR, Heer M, Hillary RP, Hoofnagle AN, Hook VYH, Jenkinson G, Jiang P, Keshavarzian A, Laurie SS, Lee-McMullen B, Lumpkins SB, MacKay M, Maienschein-Cline MG, Melnick AM, Moore TM, Nakahira K, Patel HH, Pietrzyk R, Rao V, Saito R, Salins DN, Schilling JM, Sears DD, Sheridan CK, Stenger MB, Tryggvadottir R, Urban AE, Vaisar T, van Espen B, Zhang J, Ziegler MG, Zwart SR, Charles JB, Kundrot CE, Scott GBI, Bailey SM, Basner M, Feinberg AP, Lee SMC, Mason CE, Mignot E, Rana BK, Smith SM, Snyder MP, Turek FW (2019) The NASA Twins Study: a multidimensional analysis of a year-long human spaceflight. Science. https://doi.org/10.1126/science.aau8650
Lange CE, Niama FR, Cameron K, Olson SH, Aime Nina R, Ondzie A, Bounga G, Smith BR, Pante J, Reed P, Tamufe U, Laudisoit A, Goldstein T, Bagamboula MPassi, R. & Joly, D. O. (2019) First evidence of a new simian adenovirus clustering with human mastadenovirus F viruses. Virol J 16:147
Zerboni L, Sen N, Oliver SL, Arvin AM (2014) Molecular mechanisms of varicella zoster virus pathogenesis. Nat Rev Microbiol 12:197–210
Krug LT, Pellett PE (2014) Roseolovirus molecular biology: recent advances. Curr Opin Virol 9:170–177
Lozano-Lozano M, Fernández-Lao C, Cantarero-Villanueva I, Noguerol I, Álvarez-Salvago F, Cruz-Fernández M, Arroyo-Morales M, Galiano-Castillo N (2020) A blended learning system to improve motivation, mood state, and satisfaction in undergraduate students: randomized controlled trial. J Med Internet Res 22:e17101
World Health Organization (2014) Infection prevention and control of epidemic-and pandemic-prone acute respiratory infections in health care. World Health Organization, Geneva
Siegel JD, Healthcare Infection Control Practices Advisory Committee (2007) 2007 Guideline for isolation precautions: preventing transmission of infectious agents in healthcare settings. Am J Inf Control 35(10):S65–S164
Randall K, Ewing ET, Marr LC, Jimenez JL, Bourouiba L (2021) How did we get here: what are droplets and aerosols and how far do they go? A historical perspective on the transmission of respiratory infectious diseases. Interface Focus. https://doi.org/10.1098/rsfs.2021.0049
Darquenne C (2014) Aerosol deposition in the human lung in reduced gravity. J Aerosol Med Pulm Drug Deliv 27:170–177
Darquenne C (2020) Deposition mechanisms. J Aerosol Med Pulm Drug Deliv 33:181–185
Darquenne C, Zeman KL, Sá RC, Cooper TK, Fine JM, Bennett WD, Prisk GK (2013) Removal of sedimentation decreases relative deposition of coarse particles in the lung periphery. J Appl Physiol 115:546–555
Prisk GK (2014) Microgravity and the respiratory system. Eur Respir J 43:1459–1471
Crucian B, Stowe R, Mehta S, Uchakin P, Quiriarte H, Pierson D, Sams C (2013) Immune system dysregulation occurs during short duration spaceflight on board the space shuttle. J Clin Immunol 33:456–465
Cohrs RJ, Mehta SK, Schmid DS, Gilden DH, Pierson DL (2008) Asymptomatic reactivation and shed of infectious varicella zoster virus in astronauts. J Med Virol 80:1116–1122
Crucian B, Stowe RP, Mehta S, Quiriarte H, Pierson D, Sams C (2015) Alterations in adaptive immunity persist during long-duration spaceflight. NPJ Microgravity 1:15013
Al-Benna S (2021) Negative pressure rooms and COVID-19. J Perioper Pract 31:18–23
Honda T, Nakayama R, Kawahara Y, Yuge L, Ueda K (2020) Kaposi’s sarcoma-associated herpesvirus is cell-intrinsically controlled in latency in microgravity. Virus Res 276:197821
Taylor P (2015) Impact of space flight on bacterial virulence and antibiotic susceptibility. Infect Drug Resist. https://doi.org/10.2147/IDR.S67275
Unoarumhi Y, Blumenthal RM, Matson JS (2016) Evolution of a global regulator: Lrp in four orders of γ-Proteobacteria. BMC Evol Biol 16:111
Hammond TG, Stodieck L, Koenig P, Hammond JS, Gunter MA, Allen PL, Birdsall HH (2016) Effects of microgravity and clinorotation on the virulence of Klebsiella, Streptococcus, Proteus, and Pseudomonas. Gravitational Space Res 4:39–50
Urbaniak C, Morrison MD, Thissen JB, Karouia F, Smith DJ, Mehta S, Jaing C, Venkateswaran K (2022) Microbial tracking-2, a metagenomics analysis of bacteria and fungi onboard the International Space Station. Microbiome 10:100
Costea PI, Zeller G, Sunagawa S, Pelletier E, Alberti A, Levenez F, Tramontano M, Driessen M, Hercog R, Jung F-E, Kultima JR, Hayward MR, Coelho LP, Allen-Vercoe E, Bertrand L, Blaut M, Brown JRM, Carton T, Cools-Portier S, Daigneault M, Derrien M, Druesne A, de Vos WM, Finlay BB, Flint HJ, Guarner F, Hattori M, Heilig H, Luna RA, van HylckamaVlieg J, Junick J, Klymiuk I, Langella P, le Chatelier E, Mai V, Manichanh C, Martin JC, Mery C, Morita H, O’Toole PW, Orvain C, Patil KR, Penders J, Persson S, Pons N, Popova M, Salonen A, Saulnier D, Scott KP, Singh B, Slezak K, Veiga P, Versalovic J, Zhao L, Zoetendal EG, Ehrlich SD, Dore J, Bork P (2017) Towards standards for human fecal sample processing in metagenomic studies. Nat Biotechnol 35:1069–1076
McLaughlin J, Watterson S, Layton AM, Bjourson AJ, Barnard E, McDowell A (2019) Propionibacterium acnes and Acne vulgaris: new insights from the integration of population genetic, multi-omic. Biochem Host-Microbe Stud Microorganisms 7:128
Chabi R, Momtaz H (2019) Virulence factors and antibiotic resistance properties of the Staphylococcus epidermidis strains isolated from hospital infections in Ahvaz, Iran. Trop Med Health 47:56
George S, Muhaj FF, Nguyen CD, Tyring SK (2022) Part I Antimicrobial resistance: bacterial pathogens of dermatologic significance and implications of rising resistance. J Am Acad Dermatol 86:1189–1204
Beirne C, McCann E, McDowell A, Miliotis G (2022) Genetic determinants of antimicrobial resistance in three multi-drug resistant strains of Cutibacterium acnes isolated from patients with acne: a predictive in silico study. Access Microbiol. https://doi.org/10.1099/acmi.0.000404
Venkateswaran K, Singh NK, Checinska Sielaff A, Pope RK, Bergman NH, van Tongeren SP, Patel NB, Lawson PA, Satomi M, Williamson CHD, Sahl JW, Keim P, Pierson D, Perry J (2017) Non-toxin-producing Bacillus cereus strains belonging to the B. anthracis clade isolated from the International Space Station. mSystems. https://doi.org/10.1128/mSystems.00021-17
Daudu R, Singh NK, Wood JM, Debieu M, O’Hara NB, Mason CE, Venkateswaran K (2020) Draft genome sequences of Bacillaceae strains isolated from the International Space Station. Microbiol Resour Announc. https://doi.org/10.1128/MRA.00701-20
Hagan AK, Tripathi A, Berger D, Sherman DH, Hanna PC (2017) Petrobactin is exported from Bacillus anthracis by the RND-type Exporter ApeX. MBio. https://doi.org/10.1128/mBio.01686-17
Liu X, Ding S, Shi P, Dietrich R, Märtlbauer E, Zhu K (2017) Non-hemolytic enterotoxin of Bacillus cereus induces apoptosis in Vero cells. Cell Microbiol 19:e12684
Ikeda M, Yagihara Y, Tatsuno K, Okazaki M, Okugawa S, Moriya K (2015) Clinical characteristics and antimicrobial susceptibility of Bacillus cereus blood stream infections. Ann Clin Microbiol Antimicrob 14:43
Singh NK, Wood JM, Mhatre SS, Venkateswaran K (2019) Metagenome to phenome approach enables isolation and genomics characterization of Kalamiella piersonii gen. nov., sp. nov. from the International Space Station. Appl Microbiol Biotechnol 103:4483–4497
Madrigal P, Singh NK, Wood JM, Gaudioso E, Hernández-del-Olmo F, Mason CE, Venkateswaran K, Beheshti A (2022) Machine learning algorithm to characterize antimicrobial resistance associated with the International Space Station surface microbiome. Microbiome 10:134
Rekha PD, Hameed A, Manzoor MAP, Suryavanshi MV, Ghate SD, Arun AB, Rao SS, Athmika, Bajire SK, Mujeeburahiman M, Young C-C (2020) First report of pathogenic bacterium Kalamiella piersonii isolated from urine of a kidney stone patient: draft genome and evidence for role in struvite crystallization. Pathogens 9:711
Alpizar-Rivas R, Cameron A, Hay CM (2022) Human disease caused by Kalamiella piersonii. Ann Internal Med Clin Cases. https://doi.org/10.7326/aimcc.2022.0220
McDonagh F, Singh NK, Venkateswaran K, Lonappan AM, Hallahan B, Tuohy A, Burke L, Kovarova A, Miliotis G (2023) First complete genome of a multidrug-resistant strain of the novel human pathogen Kalamiella piersonii (GABEKP28) identified in human saliva. J Glob Antimicrob Resist 32:31–34
World Health Organization (2017) Prioritization of pathogens to guide discovery, research and development of new antibiotics for drug-resistant bacterial infections, including tuberculosis. Who, Geneva
Xu L, Sun X, Ma X (2017) Systematic review and meta-analysis of mortality of patients infected with carbapenem-resistant Klebsiella pneumoniae. Ann Clin Microbiol Antimicrob 16:18
Solomon SA, Bharadwaj AR, Singh NK, Wood JM, Debieu M, O’Hara NB, Mason CE, Venkateswaran K (2020) Draft genome sequences of Klebsiella species isolated from the International Space Station. Microbiol Resour Announc. https://doi.org/10.1128/MRA.00923-20
Nogueira MF, Pereira L, Jenull S, Kuchler K, Lion T (2019) Klebsiella pneumoniae prevents spore germination and hyphal development of Aspergillus species. Sci Rep 9:218
Pati NB, Doijad SP, Schultze T, Mannala GK, Yao Y, Jaiswal S, Ryan D, Suar M, Gwozdzinski K, Bunk B, Mraheil MA, Marahiel MA, Hegemann JD, Spröer C, Goesmann A, Falgenhauer L, Hain T, Imirzalioglu C, Mshana SE, Overmann J, Chakraborty T (2018) Enterobacter bugandensis: a novel enterobacterial species associated with severe clinical infection. Sci Rep 8:5392
Singh NK, Bezdan D, Checinska Sielaff A, Wheeler K, Mason CE, Venkateswaran K (2018) Multi-drug resistant Enterobacter bugandensis species isolated from the International Space Station and comparative genomic analyses with human pathogenic strains. BMC Microbiol 18:175
Bouza E (2002) Klebsiella and Enterobacter: antibiotic resistance and treatment implications. Semin Respir Infect 17:215–230
Chen C-J, Lu P-L, Jian S-H, Fu H-L, Huang P-H, Chang C-Y (2022) Molecular epidemiology, risk factors and clinical outcomes of carbapenem-nonsusceptible Enterobacter cloacae complex infections in a Taiwan University Hospital. Pathogens 11:151
Kaper JB, Nataro JP, Mobley HLT (2004) Pathogenic Escherichia coli. Nat Rev Microbiol 2:123–140
Sadek M, Saad AM, Nordmann P, Poirel L (2022) Genomic characterization of an extensively drug-resistant extra-intestinal pathogenic (ExPEC) Escherichia coli clinical isolate co-producing two carbapenemases and a 16S rRNA methylase. Antibiotics 11:1479
Alhashash F, Weston V, Diggle M, McNally A (2013) Multidrug-resistant Escherichia coli bacteremia. Emerg Infect Dis. https://doi.org/10.3201/eid1910.130309
Padgen MR, Chinn TN, Friedericks CR, Lera MP, Chin M, Parra MP, Piccini ME, Ricco AJ, Spremo SM (2020) The EcAMSat fluidic system to study antibiotic resistance in low earth orbit: development and lessons learned from space flight. Acta Astronaut 173:449–459
Padgen MR, Lera MP, Parra MP, Ricco AJ, Chin M, Chinn TN, Cohen A, Friedericks CR, Henschke MB, Snyder TV, Spremo SM, Wang J-H, Matin AC (2020) EcAMSat spaceflight measurements of the role of σs in antibiotic resistance of stationary phase Escherichia coli in microgravity. Life Sci Space Res (Amst) 24:18–24
Aunins TR, Erickson KE, Prasad N, Levy SE, Jones A, Shrestha S, Mastracchio R, Stodieck L, Klaus D, Zea L, Chatterjee A (2018) Spaceflight modifies Escherichia coli gene expression in response to antibiotic exposure and reveals role of oxidative stress response. Front Microbiol. https://doi.org/10.3389/fmicb.2018.00310
Zea L, Larsen M, Estante F, Qvortrup K, Moeller R, Dias de Oliveira S, Stodieck L, Klaus D (2017) Phenotypic changes exhibited by E. coli cultured in space. Front Microbiol. https://doi.org/10.3389/fmicb.2017.01598
Wilson JW, Ott CM, Zu Bentrup KH, Ramamurthy R, Quick L, Porwollik S, Cheng P, McClelland M, Tsaprailis G, Radabaugh T, Hunt A, Fernandez D, Richter E, Shah M, Kilcoyne M, Joshi L, Nelman-Gonzalez M, Hing S, Parra M, Dumars P, Norwood K, Bober R, Devich J, Ruggles A, Goulart C, Rupert M, Stodieck L, Stafford P, Catella L, Schurr MJ, Buchanan K, Morici L, McCracken J, Allen P, Baker-Coleman C, Hammond T, Vogel J, Nelson R, Pierson DL, Stefanyshyn-Piper HM, Nickerson CA (2007) Space flight alters bacterial gene expression and virulence and reveals a role for global regulator Hfq. Proc Natl Acad Sci 104:16299–16304
Singh NK, Wood JM, Mhatre SS, Venkateswaran K (2019) Correction to: metagenome to phenome approach enables isolation and genomics characterization of Kalamiella piersonii gen. nov., sp. nov. from the International Space Station. Appl Microbiol Biotechnol 103:6851–6852
Barrila J, Sarker SF, Hansmeier N, Yang S, Buss K, Briones N, Park J, Davis RR, Forsyth RJ, Ott CM, Sato K, Kosnik C, Yang A, Shimoda C, Rayl N, Ly D, Landenberger A, Wilson SD, Yamazaki N, Steel J, Montano C, Halden RU, Cannon T, Castro-Wallace SL, Nickerson CA (2021) Evaluating the effect of spaceflight on the host–pathogen interaction between human intestinal epithelial cells and Salmonella typhimurium. NPJ Microgravity 7:9
Zhang B, Bai P, Zhao X, Yu Y, Zhang X, Li D, Liu C (2019) Increased growth rate and amikacin resistance of Salmonella enteritidis after one-month spaceflight on China’s Shenzhou-11 spacecraft. MicrobiologyOpen. https://doi.org/10.1002/mbo3.833
Kim SB, Jeon YD, Kim JH, Kim JK, Ann HW, Choi H, Kim MH, Song JE, Ahn JY, Jeong SJ, Ku NS, Han SH, Choi JY, Song YG, Kim JM (2015) Risk factors for mortality in patients with Serratia marcescens bacteremia. Yonsei Med J 56:348
Bai P, Zhang B, Zhao X, Li D, Yu Y, Zhang X, Huang B, Liu C (2019) Decreased metabolism and increased tolerance to extreme environments in Staphylococcus warneri during long-term spaceflight. MicrobiologyOpen. https://doi.org/10.1002/mbo3.917
Kamath U, Singer C, Isenberg HD (1992) Clinical significance of Staphylococcus warneri bacteremia. J Clin Microbiol 30:261–264
Kanuparthy A, Challa T, Meegada S, Siddamreddy S, Muppidi V (2020) Staphylococcus warneri: skin commensal and a rare cause of urinary tract infection. Cureus. https://doi.org/10.7759/cureus.8337
Nickerson CA, Ott CM, Mister SJ, Morrow BJ, Burns-Keliher L, Pierson DL (2000) Microgravity as a novel environmental signal affecting Salmonella enterica serovar typhimurium virulence. Infect Immun 68:3147–3152
Hammond TG, Stodieck L, Birdsall HH, Becker JL, Koenig P, Hammond JS, Gunter MA, Allen PL (2013) Effects of microgravity on the virulence of Listeria monocytogenes, Enterococcus faecalis, Candida albicans, and methicillin-resistant Staphylococcus aureus. Astrobiology 13:1081–1090
Fairén AG, Parro V, Schulze-Makuch D, Whyte L (2017) Searching for life on mars before it is too late. Astrobiology 17:962–970
Zhao X, Yu Y, Zhang X, Huang B, Bai P, Xu C, Li D, Zhang B, Liu C (2019) Decreased biofilm formation ability of Acinetobacter baumannii after spaceflight on China’s Shenzhou 11 spacecraft. MicrobiologyOpen. https://doi.org/10.1002/mbo3.763
Bai P, Li Y, Bai J, Xu H (2022) Markedly decreased growth rate and biofilm formation ability of Acinetobacter schindleri after a long-duration (64 days) spaceflight. Eur Rev Med Pharmacol Sci 26:4001–4015
Lawal A, Jejelowo OA, Rosenzweig JA (2010) The effects of low-shear mechanical stress on Yersinia pestis virulence. Astrobiology 10:881–888
Urbaniak C, Sielaff AC, Frey KG, Allen JE, Singh N, Jaing C, Wheeler K, Venkateswaran K (2018) Detection of antimicrobial resistance genes associated with the International Space Station environmental surfaces. Sci Rep 8:814
Tirumalai MR, Karouia F, Tran Q, Stepanov VG, Bruce RJ, Ott CM, Pierson DL, Fox GE (2019) Evaluation of acquired antibiotic resistance in Escherichia coli exposed to long-term low-shear modeled microgravity and background antibiotic exposure. MBio. https://doi.org/10.1128/mBio.02637-18
Tirumalai MR, Karouia F, Tran Q, Stepanov VG, Bruce RJ, Ott CM, Pierson DL, Fox GE (2017) The adaptation of Escherichia coli cells grown in simulated microgravity for an extended period is both phenotypic and genomic. NPJ Microgravity 3:15
van Ombergen A, Rossiter A, Ngo-Anh TJ (2021) ‘White Mars’—nearly two decades of biomedical research at the Antarctic Concordia station. Exp Physiol 106:6–17
Schiwon K, Arends K, Rogowski KM, Fürch S, Prescha K, Sakinc T, van Houdt R, Werner G, Grohmann E (2013) Comparison of antibiotic resistance, biofilm formation and conjugative transfer of Staphylococcus and Enterococcus isolates from International Space Station and Antarctic Research Station Concordia. Microb Ecol 65:638–651
Beuls E, van Houdt R, Leys N, Dijkstra C, Larkin O, Mahillon J (2009) Bacillus thuringiensis conjugation in simulated microgravity. Astrobiology 9:797–805
de Boever P, Mergeay M, Ilyin V, Forget-Hanus D, van der Auwera G, Mahillon J (2007) Conjugation-mediated plasmid exchange between bacteria grown under space flight conditions. Microgravity Sci Technol 19:138–144
Novikova N, de Boever P, Poddubko S, Deshevaya E, Polikarpov N, Rakova N, Coninx I, Mergeay M (2006) Survey of environmental biocontamination on board the International Space Station. Res Microbiol 157:5–12
Urbaniak C, Grams T, Mason CE, Venkateswaran K (2021) Simulated microgravity promotes horizontal gene transfer of antimicrobial resistance genes between bacterial genera in the absence of antibiotic selective pressure. Life 11:960
Checinska Sielaff A, Urbaniak C, Mohan GBM, Stepanov VG, Tran Q, Wood JM, Minich J, McDonald D, Mayer T, Knight R, Karouia F, Fox GE, Venkateswaran K (2019) Characterization of the total and viable bacterial and fungal communities associated with the International Space Station surfaces. Microbiome 7:50
Knox BP, Blachowicz A, Palmer JM, Romsdahl J, Huttenlocher A, Wang CCC, Keller NP, Venkateswaran K (2016) Characterization of Aspergillus fumigatus isolates from air and surfaces of the International Space Station. mSphere. https://doi.org/10.1128/mSphere.00227-16
Singh NK, Blachowicz A, Checinska A, Wang C, Venkateswaran K (2016) Draft genome sequences of two Aspergillus fumigatus strains, isolated from the International Space Station. Genome Announc. https://doi.org/10.1128/genomeA.00553-16
Romsdahl J, Blachowicz A, Chiang AJ, Singh N, Stajich JE, Kalkum M, Venkateswaran K, Wang CCC (2018) Characterization of Aspergillus niger Isolated from the International Space Station. mSystems. https://doi.org/10.1128/mSystems.00112-18
Nielsen S, White K, Preiss K, Peart D, Gianoulias K, Juel R, Sutton J, McKinney J, Bender J, Pinc G, Bergren K, Gans W, Kelley J, McQuaid M (2021) Growth and antifungal resistance of the pathogenic yeast, Candida albicans, in the microgravity environment of the International Space Station: an aggregate of multiple flight experiences. Life 11:283
Zhang Y, Zhang X, Zhang J, Ali S, Wu J (2022) Spaceflight changes the production and bioactivity of secondary metabolites in Beauveria bassiana. Toxins (Basel) 14:555
Urbaniak C, Massa G, Hummerick M, Khodadad C, Schuerger A, Venkateswaran K (2018) Draft genome sequences of two Fusarium oxysporum isolates cultured from infected Zinnia hybrida plants grown on the International Space Station. Genome Announc. https://doi.org/10.1128/genomeA.00326-18
Urbaniak C, van Dam P, Zaborin A, Zaborina O, Gilbert JA, Torok T, Wang CCC, Venkateswaran K (2019) Genomic characterization and virulence potential of two Fusarium oxysporum isolates cultured from the International Space Station. mSystems. https://doi.org/10.1128/mSystems.00345-18
Romsdahl J, Blachowicz A, Chiang AJ, Chiang Y-M, Masonjones S, Yaegashi J, Countryman S, Karouia F, Kalkum M, Stajich JE, Venkateswaran K, Wang CCC (2019) International Space Station conditions alter genomics, proteomics, and metabolomics in Aspergillus nidulans. Appl Microbiol Biotechnol 103:1363–1377
Guo J, Han N, Zhang Y, Wang H, Zhang X, Su L, Liu C, Li J, Chen C, Liu C (2015) Use of genome sequencing to assess nucleotide structure variation of Staphylococcus aureus strains cultured in spaceflight on Shenzhou-X, under simulated microgravity and on the ground. Microbiol Res 170:61–68
Romsdahl J, Blachowicz A, Chiang Y-M, Venkateswaran K, Wang CCC (2020) Metabolomic analysis of Aspergillus niger isolated from the International Space Station reveals enhanced production levels of the antioxidant Pyranonigrin A. Front Microbiol 11:931
Blachowicz A, Romsdahl J, Chiang AJ, Masonjones S, Kalkum M, Stajich JE, Torok T, Wang CCC, Venkateswaran K (2022) The International Space Station environment triggers molecular responses in Aspergillus niger. Front Microbiol 13:893071
Schuerger AC, Amaradasa BS, Dufault NS, Hummerick ME, Richards JT, Khodadad CL, Smith TM, Massa GD (2021) Fusarium oxysporum as an opportunistic fungal pathogen on Zinnia hybrida plants grown on board the International Space Station. Astrobiology 21:1029–1048
Bijlani S, Singh NK, Eedara VVR, Podile AR, Mason CE, Wang CCC, Venkateswaran K (2021) Methylobacterium ajmalii sp. nov., isolated from the International Space Station. Front Microbiol. https://doi.org/10.3389/fmicb.2021.639396
van der Putten WH, Klironomos JN, Wardle DA (2007) Microbial ecology of biological invasions. ISME J 1:28–37
Wingfield MJ, Hammerbacher A, Ganley RJ, Steenkamp ET, Gordon TR, Wingfield BD, Coutinho TA (2008) Pitch canker caused by Fusarium circinatum—a growing threat to pine plantations and forests worldwide. Australas Plant Pathol 37:319–334
Rentería-Solís Z, Birka S, Schmäschke R, Król N, Obiegala A (2018) First detection of Baylisascaris procyonis in wild raccoons (Procyon lotor) from Leipzig, Saxony, Eastern Germany. Parasitol Res 117:3289–3292
Seebens H, Blackburn TM, Dyer EE, Genovesi P, Hulme PE, Jeschke JM, Pagad S, Pyšek P, Winter M, Arianoutsou M (2017) No saturation in the accumulation of alien species worldwide. Nat Commun 8:1–9
Chinchio E, Crotta M, Romeo C, Drewe JA, Guitian J, Ferrari N (2020) Invasive alien species and disease risk: an open challenge in public and animal health. PLoS Pathog 16:e1008922
Landis GA (2020) Settling venus: a city in the clouds? In: ASCEND 2020. American Institute of Aeronautics and Astronautics. https://doi.org/10.2514/6.2020-4152
Affholder A, Guyot F, Sauterey B, Ferrière R, Mazevet S (2021) Bayesian analysis of Enceladus’s plume data to assess methanogenesis. Nat Astron 5:805–814
Crawford IA, Cockell CS (2010) Astrobiology on the Moon. Astron Geophys 51:411–414
Gronstal A, Cockell CS, Perino MA, Bittner T, Clacey E, Clark O, Ingold O, Alves de Oliveira C, Wathiong S (2007) Lunar astrobiology: a review and suggested laboratory equipment. Astrobiology 7:767–782
Wu Z, Ling Z, Zhang J, Fu X, Liu C, Xin Y, Li B, Qiao L (2021) A mars environment chamber coupled with multiple in situ spectral sensors for mars exploration. Sensors 21:2519
Sobrado JM, Martín-Soler J, Martín-Gago JA (2014) Mimicking mars: a vacuum simulation chamber for testing environmental instrumentation for mars exploration. Rev Sci Instrum 85:035111
Berry BJ, Jenkins DG, Schuerger AC (2010) Effects of simulated mars conditions on the survival and growth of Escherichia coli and Serratia liquefaciens. Appl Environ Microbiol 76:2377–2386
Blachowicz A, Mayer T, Bashir M, Pieber TR, de León P, Venkateswaran K (2017) Human presence impacts fungal diversity of inflated lunar/mars analog habitat. Microbiome 5:62
Chowdhary A, Perfect J, de Hoog GS (2015) Black molds and melanized yeasts pathogenic to humans. Cold Spring Harb Perspect Med 5:a019570
Valenzuela-Lopez N, Martin-Gomez MT, Los-Arcos I, Stchigel AM, Guarro J, Cano-Lira JF (2021) A new pleosporalean fungus isolated from superficial to deep human clinical specimens. Med Mycol 59:278–288
Schubert K, Groenewald JZ, Braun U, Dijksterhuis J, Starink M, Hill CF, Zalar P, de Hoog GS, Crous PW (2007) Biodiversity in the Cladosporium herbarum complex (Davidiellaceae, Capnodiales), with standardisation of methods for Cladosporium taxonomy and diagnostics. Stud Mycol 58:105–156
Bauer M, Wickenhauser C, Haak A, Pazaitis N, Siebolts U, Mawrin C, Strauss C, Rickerts V, Stoevesandt D, Cornely OA, Meis JF, Hagen F (2018) Case report: a fatal case of cryptococcosis in an immunocompetent patient due to Cryptococcus deuterogattii (AFLP6/VGII). JMM Case Rep. https://doi.org/10.1099/jmmcr.0.005168
McKay CP (2010) An origin of life on mars. Cold Spring Harb Perspect Biol 2:a003509–a003509
Horne WH, Volpe RP, Korza G, DePratti S, Conze IH, Shuryak I, Grebenc T, Matrosova VY, Gaidamakova EK, Tkavc R, Sharma A, Gostinčar C, Gunde-Cimerman N, Hoffman BM, Setlow P, Daly MJ (2022) Effects of desiccation and freezing on microbial ionizing radiation survivability: considerations for mars sample return. Astrobiology 22:1337–1350
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McDonagh, F., Cormican, M., Morris, D. et al. Medical Astro-Microbiology: Current Role and Future Challenges. J Indian Inst Sci 103, 771–796 (2023). https://doi.org/10.1007/s41745-023-00360-1
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DOI: https://doi.org/10.1007/s41745-023-00360-1