Keywords

1 Introduction

The number of bacterial species living in all biospheres may exceed one million, and majority of them are harmless or beneficial to humans. A larger number of species are opportunistic pathogens, which only in certain conditions cause human diseases; and several more are just a part of the normal human flora, not linked to diseases. With the aim of treating infectious diseases and limiting microbial proliferation, antimicrobial agents are being developed. Many organisms produce their own antimicrobials for self-defense that protect them from other microbes concurrently existing in the same milieu. For the treatment of different infectious diseases, many of these innate antimicrobial agents are characterized, studied, and modified extensively to enhance the activity (Munita and Arias 2016; Aslam et al. 2018). Some of the antimicrobial agents are very specific to pathogens or have broad-spectrum activity affecting a wide range of microbes.

The discovery and use of antimicrobial agents have brought a big transformation in the infection management, but simultaneously generated resistance as an adaptive response in microbes (Cleveland et al. 2012; Alexander et al. 2013; Vale-Silva and Sanglard 2015; Alareqi et al. 2016; Lima et al. 2016; Brinkac et al. 2017). This mechanism is often due to acquired resistance from the same or other bacterial species, whereas in some, innate resistance plays a considerable role in antimicrobial resistance (AMR).

AMR dates centuries back, as footprint of tetracycline has been described from the skeletons of Sudanese Nubia (350–500 AD) (Bassett et al. 1980). Several antimicrobial resistance genes (ARGs) have been testified from microbiota of an eleventh-century mummy (Santiago-Rodriguez et al. 2015), millions of years-old caves, and ancient permafrost sediment (D’Costa et al. 2011; Bhullar et al. 2012). AMR is considered as one of the most important public health concerns of the twenty-first century by the World Health Organization (WHO) and has been a cause of huge economic burden globally (Munita and Arias 2016; Aslam et al. 2018). AMR bacteria infect about two million people, causing 23,000 deaths each year in the United States (Li and Webster 2018). In Europe, the fatal number is approximately 25,000 due to antibiotic resistance (Brinkac et al. 2017). Misuse or uncontrolled use of antibiotics in clinical settings is linked to rise in AMR in microbes.

AMR is common in the microbial community and has evolved with different defense and adaptive mechanisms with time (Martinez 2009; Davies and Davies 2010; Leisner et al. 2016). Several species of bacteria have remarkable genomic plasticity that helps them to survive and compete in response to antimicrobial molecules produced by the other microbes. Due to genomic plasticity, bacteria are flexible enough to use several different genetic mechanisms like mutation, horizontal gene transfer (HGT) to adopt or survive the action of antimicrobials (Fletcher 2015), and/or a wide range of adverse environmental factors. The presence of more than one ARG coupled with other factors leads to multidrug resistance (MDR).

Recently, many studies have reported the role of the environment as an important reservoir and in transmission of resistance (Martínez 2008; Wright 2010; Ashbolt et al. 2013; Bondarczuk et al. 2016; Hiltunen et al. 2017; Bengtsson-Palme et al. 2018). An increase in the level of antimicrobial-resistant bacteria (ARB) carrying ARGs, especially in water and wastewater, has been reported in several studies (Rizzo et al. 2013; Devarajan et al. 2015; Sharma et al. 2016; Li et al. 2017). The increasing concentration of ARB in different environmental niches like soil and industrial and farming wastewater is a potential threat to the ecosystems (Devarajan et al. 2015), which eventually enters the human food chain through different vectors.

Some of the ARGs found in pathogens are thought to have originated from bacteria mostly present in the external environment that exist as a result of conjugation, where genetic materials are transferred from cell to cell or acquiring genetic material from the virus by transduction (Martínez 2012; Wellington et al. 2013). After the gene-acquiring process, a microbe can transform itself by incorporating exogenous DNA from the environment into its own genome. Mobile genetic elements (MGEs) that often contain ARGs can spread very effectively between unrelated species. All these events are initiated to a certain extent due to selective forces exerted by antibiotics both in clinical and natural environmental sources like infection site, soil, water, and manure used in agriculture, which in turn results in maintenance and spread of antibiotic resistance (Huang et al. 2012; Ashbolt et al. 2013; Berendonk et al. 2015; He et al. 2016). Many findings suggest chemicals other than antibiotics also act as selective factors in stimulating AMR, which include heavy metals (Baker-Austin et al. 2006; Seiler and Berendonk 2012), pesticides (Rangasamy et al. 2018; Ramakrishnan et al. 2019), nano-materials (Qiu et al. 2012; Ding et al. 2016), disinfectants (Guo et al. 2015; Zhang et al. 2017), cosmetics (Orús et al. 2015), and disinfection derivatives (Lv et al. 2015; Li et al. 2016). Heavy metals are naturally present in the environment, and studies have proved that anthropogenic activities accelerate the release and deposition of metals in various environments (Seiler and Berendonk 2012; Rodríguez Martín et al. 2015; Wang et al. 2015; Zhang et al. 2015; Zhang et al. 2018).

The decrease in the antibiotic use directly prevents the spread and maintenance of antibiotic resistance in clinical and in environmental settings (Salyers and Amábile-Cuevas 1997). The other factors like deposition of heavy metals from manure, anthropogenic chemicals, and micro−/nanoplastic molecules should be taken into consideration and managed accordingly. This chapter reviews different environmental factors that support in the increase of AMR.

2 Environmental Factors

It is well documented that antibiotic resistance is a serious health concern (Pruden et al. 2006; Peak et al. 2007; Munir et al. 2011), and an increase in the spread of the ARGs is directly responsible for the emergence of resistant bacteria. The upsurge and dissemination of the ARGs are directly associated with the constant antibiotic pressure. AMR bacteria are stimulated and signaled to transfer ARGs to other bacteria with the help of MGEs (Allen et al. 2010; Rizzo et al. 2013). With advancement of time, researchers have detected considerable rise in the level of ARGs even in the absence of antibiotic pressure (Alonso et al. 2001; Ji et al. 2012). Studies have also been conducted to identify other chemicals responsible for selecting or supporting AMR in several bacterial populations. In many of these studies, it was established that substances other than antibiotics, such as heavy metals, pesticides, detergents, microplastics, and cosmetics, could also support the spread of ARGs (Alonso et al. 2001; Baker-Austin et al. 2006; Ji et al. 2012). Several studies have successfully established the relationships between heavy metals and ARG abundance in diverse environmental compartments like soil (Zhao et al. 2019), different types of animal manure, and water (Zhao et al. 2018; Sui et al. 2019). Different factors and anthropogenic activities that drive antimicrobial resistance are discussed below.

2.1 Heavy Metals

In the environment, heavy metals are naturally present in abundance or deposited by various human activities. Some of these heavy metals are required in trace amounts for several cellular functions. Metals are divided into four groups based on our health requirements (Kochare and Tamir 2015): (1) Essential metals, also known as the micronutrients, are required for cellular functions; and they are the components for DNA and RNA polymerase, e.g., copper (Cu), zinc (Zn), cobalt (Co), chromium (Cr), manganese (Mn), and iron (Fe). (2) Nonessential metals, e.g., barium (Ba), aluminum (Al), and lithium (Li); (3) less toxic metals, e.g., tin (Sn) and aluminum (Al); and (4) highly toxic metals, e.g., mercury (Hg), cadmium (Cd), and arsenic (As), are considered as cellular toxins as they can form harmful complexes. Heavy metals from the environment interact with microorganisms and induce the development of resistance.

The mechanisms underlying microbial resistance to antimicrobials are for self-defense or expressed in response to other antibiotics/chemicals which are broadly classified under four different categories (Krulwich et al. 2005; Baker-Austin et al. 2006): (1) reduction of membrane permeability, (2) inactivation of the antibiotic molecules, (3) rapid efflux of the antibiotic, and/or (4) mutation of cellular targets. Microbes adopt almost similar resistance mechanisms for heavy metals as well as antimicrobials (Table 1). It is well known that different MGEs such as plasmids or transposons help the bacteria to get converted to AMR phenotype. One widely reported mechanism is integron, which is actively associated with gene transfer in the presence of metal ions. The stress exerted by heterogeneous metal ions leads to the selection of resistant bacteria. Heavy metals have long-term selection pressure on ARGs compared to antibiotics because of their nonbiodegradable nature (Stepanauskas et al. 2005). Recent studies have shown that an increase of ARGs is related to the presence of Cu and Ni in soil samples (Hu et al. 2016, 2017). Oxides of Cu, Zn, and Cd at higher concentrations have shown to increase the rate of horizontal gene transfer (HGT) but decrease conjugational transfer (Martinez et al. 2006; Suzuki et al. 2012). Few other studies have shown the increase of conjugational transfer and HGT even at sublethal concentrations, but with a different mechanism (Jutkina et al. 2018; Zhang et al. 2018).

Table 1 Similar resistance mechanisms exhibited by microbes in response to metals or antibiotics
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Several reports emphasize the importance of co-occurrence of AMR and resistance to metals in the same bacteria. When a metabolic pathway is activated as a defense mechanism in response to two different antimicrobials, it is termed as a cross-reaction (Baker-Austin et al. 2006; Zhu et al. 2013; Poole 2017; Ding et al. 2019) (Fig. 1). An example of a cross-reaction is an efflux pump, in which several MDR efflux pumps help microbes sustain exposure to both antibiotics and heavy metals. In the co-resistance category, the ARGs and metal resistance genes (MRGs) are positioned on the same genetic element like integrons, plasmids, or transposons (Fig. 2). Co-resistance has been reported in Salmonella enterica serotype abortus equi that showed resistance to ampicillin, arsenic, chromium, cadmium, and mercury positioned in a plasmid (Ghosh et al. 2000). Removal of this plasmid makes the strain susceptible to ampicillin and all the metals (Ghosh et al. 2000).

Fig. 1
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Co-selection of metal and antibiotic by (i) co-resistance: when resistance-conferring genes to both antibiotics and metals are located in the same genetic element. Due to this physical linkage, when one is expressed, it co-selects the other. pHCM1 plasmid is one such example where mercury resistance is linked to other antibiotic resistance genes

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Fig. 2
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Co-selection of metal and antibiotic by (ii) cross-regulation: when the same pathway is activated as a defense mechanism in response to metals or antibiotics, for example, TetA(L) efflux pump which pumps out tetracycline and heavy metal cobalt conferring cross-resistance to both metals (cobalt) and antibiotics (tetracycline)

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Heavy metals are present in all the environmental niches. Metal atoms form cations by losing electrons making them more bioavailable and express antimicrobial activity. This process is greatly influenced by several environmental conditions modified by pH, oxygen level, or concentration of organic matter. Generally, microbial toxicity of heavy metals is due to their chemical affinity for thiol groups and macro-biomolecules and also depends on the solubility of the metal compounds under physiological conditions (Lemire et al. 2013). In response to the exposure of different toxic metals, bacterial self-defense has developed a certain resistance mechanism to avoid cellular toxicity. This mechanism has been divided into four groups. (1) First is complex formation or sequestration of toxic metals (Silver and Phung 1996). By selectively binding to macromolecules as a biochemical response, the concentration of the free toxic ions in the cytoplasm is reduced. The addition of either metals or antibiotics to planktonic cells can stimulate the production of extracellular polymeric substances (EPSs), which leads to cell adhesion and ultimately the formation of a biofilm as a survival mechanism (Teitzel and Parsek 2003). Bacterial cells within biofilm can withstand a higher concentration of antimicrobial agents. The EPS matrix and the polysaccharides contained in biofilm bind toxic metals (Teitzel and Parsek 2003). As a result, tolerance of bacteria to heavy metals and antibiotics is enhanced. (2) The second mechanism is by detoxification through reduction of intracellular ions (Nies 2003). An example is mercury reductase, encoded by the merA gene. The MerA protein reduces Hg2+ ions to less toxic Hg (Schiering et al. 1991). (3) Third is excretion of toxic ions by efflux systems (Nies and Silver 1995). In this, the cation/proton antiporter Czc has been identified in Alcaligenes eutrophus that mediates resistance to the metal ions Cd2+, Zn2+, and Co2+ by removal of metals though the inner and outer membranes from the cytoplasm (Silver and Phung 1996). Genes responsible for efflux mechanism to metal resistance also confer resistance to antibiotics. (4) Fourth is change in morphology and/or pigment production. To overcome environmental change due to toxic metal contamination, a bacterial cell can undergo morphological changes and even secretes pigments. On exposure to toxic lead, Pseudomonas aeruginosa show pyoverdine and pyochelin pigment production (Naik et al. 2013).

In the environment, there is a continuous inflow of heavy metals due to anthropogenic, industrial, agricultural, or other human activities. Use of heavy metals such as Cd, Hg, Cu, and Zn in feeds, organic and inorganic fertilizers, and aquaculture substances has immensely contributed to metal contamination. Along with heavy metals, antibiotics are also used in different forms to increase agricultural or farm produce. Many studies have proved genetic exchange of resistance genes between environmental antibiotic-resistant bacteria and human pathogens sustained by the heavy metals in various environmental niches.

2.2 Pesticides

Pesticides are widely used to increase agricultural products. Improper application and storage of pesticides often contaminate plant tissues and environments that remain for a very long time. Pesticide contamination may cause changes at all levels of biological organization directly or indirectly. Terrestrial and aquatic ecosystems are polluted with pesticides due to leach-out from the agricultural fields. The presence of pesticides in these environments can induce resistance or persistence, even to degradation by the microbes. The pesticide-resistant microbes can use biofilm formation, efflux pumps, enzymes, membrane transport systems, and genetic makeup with plasmid- and chromosome-encoded catabolic genes for degradation. These pesticide degraders may also develop antimicrobial resistance as an extra functional trait (Ramakrishnan et al. 2019). Similar to heavy metal resistance genes, pesticide resistance genes are also transferred as gene clusters along with the genes crucial for antibiotic resistance. The consumption of pesticide-contaminated food products and the use of antibiotics by humans and in livestock animals have helped the development of antibiotic- and pesticide-resistant bacterial communities. Pesticide-antibiotic cross-resistance and the subsequent expansion of MDR bacteria are detailed in several reviews (Rangasamy et al. 2018; Ramakrishnan et al. 2019).

In a study, it was shown that the presence of monocrotophos insecticides in the agricultural soil led to the development of multidrug resistance among bacteria (Rangasamy et al. 2017). In the agricultural soil, Bacillus isolates were resistant against monocrotophos as well as antibiotics such as chloramphenicol, ampicillin, cefotaxime, streptomycin, and tetracycline. Involvement of plasmid in drug as well as insecticide resistance was confirmed through plasmid curing of resistant bacterial strains (Rangasamy et al. 2017). Several other studies also have proved that the MDR has been increased in phyto- and human pathogenic bacteria due to the presence of pesticides (Kurenbach et al. 2015; Patyka et al. 2016).

2.3 Anthropogenic Substances

Different anthropogenic activities lead to accumulation of substances in the environment that causes a potential rise and spread of resistant bacteria. The mode of action involved in the selection of resistant bacteria employs one or more of the mechanisms discussed before, i.e., “co-selection.” Polyaromatic hydrocarbons (PAHs) enter into the environment primarily through activities like coal pyrolysis, liquid fossil fuels, and biomass combustion (Bosch et al. 2015). Some PAHs are considered hazardous to humans with carcinogenic, mutagenic, and genotoxic effects. When exposed to PAH, metabolic activation of bacterial molecules with cytochrome P450 leads to the formation of highly reactive electrophilic species binding with DNA (Binková and Srám 2004). PAH was also responsible for causing a major shift in the composition of the soil microbial community (Yang et al. 2014; Gorovtsov et al. 2018). Proteobacteria are prevalent in a PAH-contaminated soil along with the PAH-degrading Streptomyces group. This same genus of bacteria is reported to carry ARGs (D'costa et al. 2006). Few findings indicate decreased HGT rate in the presence of PAH due to the formation of covalent bonding to the plasmids (Kang et al. 2015; Chen et al. 2017). Even when the HGT is interrupted in certain cases, the copy number of ARG can still increase with the growth of PAH-degrading bacteria (Gorovtsov et al. 2018).

2.4 Microplastics

Microplastics of ≥5.0 mm in size exist as contaminants in the environment and possess a very long half-life up to centuries (Kazmiruk et al. 2018). They are decisively made for a specific purpose (primary microplastics) or formed through natural degradation of plastics (secondary microplastics) (Rummel et al. 2017; Imran et al. 2019). Millions of tons of particles are discharged into the marine environment as industrial by-products, degraded plastic wastes, municipal wastes, fishing nets, etc. (Cole et al. 2011; Law and Thompson 2014; Keswani et al. 2016; Arias-Andres et al. 2018). Plastics causing marine pollution are mostly polyethylene (PE), polystyrene (PS), polyethylene terephthalate (PET), polyvinyl chloride (PVC), polyurethane (PUR), and polypropylene (PP) (Hidalgo-Ruz et al. 2012; Fok et al. 2017; Revel et al. 2018). Due to their very small size, microplastics are accumulated by oysters and crabs (Watts et al. 2016), get ingested by fishes, and eventually spread in the aquatic ecosystem (Nelms et al. 2018; Revel et al. 2018). Microplastics are considered as one of the most difficult pollutants to control with a long-lasting reactive surface. They can adhere to or adsorb organic matter and chemical substances like antibiotics, pesticides, heavy metals, and other xenobiotics (Hirai et al. 2011). These microplastics support colonization by different microbial species (Zettler et al. 2013; Oberbeckmann et al. 2016; Kettner et al. 2017), and these communities are collectively termed as “the plastisphere” (Keswani et al. 2016). They are also capable of changing the structure and composition of other microbial communities present in the surrounding environment (Reisser et al. 2013; Harrison et al. 2014; Oberbeckmann et al. 2014; Bryant et al. 2016).

It has been well documented that microplastics can adsorb antibiotics (sulfadiazine, ciprofloxacin, amoxicillin, trimethoprim, and tetracycline) on their surfaces and its low density often helps them get dispersed into the food chains and humans and animals (Li et al. 2018). Microplastics can vary in their physicochemical properties like specific surface area, crystallinity, and pore size distribution, which determine the adsorption capacity of each type (Li et al. 2018). It has been reported that tetracycline-containing microplastics in the soil can stimulate bacterial phage-mediated ARG dispersion (Sun et al. 2018). Increased proportion of HGT is reported among phylogenetically diverse bacteria on the microplastic surface compared to the free-living aquatic bacterial population (Arias-Andres et al. 2018). This microsurface acts as a perfect platform for selection of AMR in the presence of metal ions, antibiotics, and other pollutants.

2.5 Biocides

Biocides are used to control microbial growth; and these agents are used most commonly in antiseptics, disinfectants, and preservatives. Biocides functionally differ from antibiotics. Unlike antibiotics, which are very precise in action, biocides are formulated to act on multiple cellular targets and hence mostly used in higher concentrations compared to antibiotics. Biocides mostly disturb the bacterial membrane and react with the cell protein molecule or genetic material. Biocidal agents like alcohol target the bacterial membrane, whereas aldehydes and anionic surfactants affect the cell wall. In the case of hydrogen peroxide, acridine dyes, and chlorine compounds, it is the nucleic acid that gets affected (Davin-Regli and Pagès 2012).

The activity of biocides depends on the duration of contact time, pH, and temperature, the presence of organic matter or other interfering or enhancing materials/compounds, and the target microorganism. The most common adaptation mechanism expressed by microbes in response to biocide exposure is the activation of efflux pump, but some studies have observed an adaptive mechanism due to changes in protein synthesis only when biocide is present in low concentrations (Mutoh et al. 1999). Resistance to formaldehyde among members of Enterobacteriaceae is plasmid mediated and in P. aeruginosa is due to chromosomal elements. Both these resistant forms are quite stable to even grow at a concentration much higher than the lethal dose (Meyer and Cookson 2010). Biocides in certain isolates can upregulate efflux pumps by activating different biochemical pathways, which is reversed in the absence of biocides. Hence, the defense mechanisms expressed by the microbes to biocides raise the concern of simultaneous development of antimicrobial resistance as a co-selection mechanism as both the antibacterial molecules at certain extent use the similar resistance mechanisms (Pal et al. 2017; Jutkina et al. 2018; Wales and Davies 2015) (Table 2). One of the most commonly used biocides, triclosan, has received great attention in relation to the rise of resistant bugs. Triclosan is most commonly and widely used in disinfectants, preservatives, toothpastes, baby toys, and many other daily products (Westfall et al. 2019). It is bacteriostatic at lower concentrations, but is bactericidal at higher concentrations and causes cell death by affecting the plasma membrane. Just like antibiotics but unlike other biocides, triclosan at low concentrations acts on a specific cellular target. The most studied and mapped target site for triclosan is enoyl-acyl carrier protein reductase (FabI), an essential enzyme in bacterial fatty acid synthesis. Researchers have shown that mutations in FabI and its overexpression decrease bacterial susceptibility to triclosan (Heath et al. 1999; Slater-Radosti et al. 2001). Along with defective fatty acid synthesis, accumulation of the alarmone guanosine tetraphosphate (ppGpp) gives rise to persistent bacterial cells which show high resistance to antibiotics (Westfall et al. 2019). Another aspect that raises concern in biocide use is that some antibiotics share same target site FabI-like triclosan. The selective pressure created by its use may co-regulate resistance to both biocides and antibiotics (Ciusa et al. 2012).

Table 2 Reduced antibiotic sensitivity on exposure to low-level biocide
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2.6 Cosmetic Products

The development of AMR microorganisms is due to the selective pressure from preservatives, which are added in the cosmetic formulations mainly to inhibit the growth of microorganisms. Cosmetic products could also be a risk for the emergence and spread of AMR bacteria. Tolerance to formaldehyde donors such as diazolidinyl urea, imidazolidinyl urea, quaternium-15, sodium hydroxymethylglycinate, and DMDM hydantoin by Enterobacter gergoviae, Pseudomonas putida, and Burkholderia cepacia isolated from cosmetics products has shown cross-resistance to antibiotics (Orús et al. 2015). Reduced susceptibility to formaldehyde donors was detected in isolates along with increasing resistance to β-lactams, quinolones, rifampicin, and tetracycline. The outer membrane protein modifications and efflux mechanism activities were found to be responsible for the resistance traits (Orús et al. 2015). Chlorhexidine/chlorhexidine gluconate (CHG) has been used in disinfectants, oral care, and cosmetics. In vitro exposure of Staphylococcus aureus to sublethal concentrations of chlorhexidine showed cross-resistance to amikacin, cefepime, and tetracycline (Wu et al. 2016). Also, studies on Klebsiella pneumoniae had shown that bacterial exposure to CHG induced cross-resistance to colistin, which is used in the treatment of MDR pathogens (Wand et al. 2016).

3 Transmission of Antibiotic Resistance from the Environment to Humans

The environment is continuously exposed to different substances favoring the emergence and spread of antimicrobial-resistant bacteria. Microbes work as a reservoir for ARGs in the environment as well as the human body. Depending on the environmental conditions and other stress factors, different bacterial species remain viable and act as potential carriers. Genetic elements of the dead bacterial cells also act as probable sources of HGTs. Many human activities exert a high level of AMR transmission (Fletcher 2015). Several abiotic stress conditions directly support the emergence of AMR mechanism, which will be sustained through several genetic mechanisms including HGTs. The human microbiota is under constant pressure with several stimulating factors of AMR. Microplastics harboring AMR bacteria and/or substances that initiate different resistant mechanisms in microbes also reach the food chain.

4 Mitigation Policies

With the rise of the AMR issue globally, many strategies have been proposed based on several research to clearly understand the mechanism of AMR selection and transmission. One of the risk mitigation strategies commonly and widely focused is on minimizing the uptake of antibiotics and reducing the spread of AMR from the key environmental reservoirs like sewage, wastewater, manure, farms, and antibiotic manufacture waste. The most common mitigation method is restricting the use and release of antibiotics into the environment. The principle behind this is decreasing the antibiotic load, thereby lowering the selection pressure for ARGs which eventually controls the risk of AMR (Bengtsson-Palme and Larsson 2016). With the rise in risk of AMR globally, the number of research on the same aspect is numerous. A large number of data are also available which could be translated to administer a mitigation process (Vikesland et al. 2017).

There are uses of similar antibacterial approaches in treating human and/or animal infections, and the rise of a resistant form of bacteria can spread from one to another and eventually to the environment. Each plays an important role in the global spread of AMR. With the aim of bridging the multidisciplinary knowledge gap between humans, animals, and the environment to deal with AMR risk, a very comprehensive and multisectoral approach is “One Health,” where humans, animals, and the environment are considered as one. Under this initiative, the WHO, Food and Agriculture Organization (FAO) of the United Nations, World Organisation for Animal Health (OIE), Centers for Disease Control and Prevention (CDC), United States Department of Agriculture (USDA), National Oceanic and Atmospheric Administration (NOAA), and US National Environmental Health Association (NEHA) all work together in minimizing the risk of rise and spread of AMR. But it is to be remembered that there are also other selection pressures simultaneously present in the environment responsible for ARG and AMR pool, proper understanding of which is also required.

5 Conclusion

The rise of antibiotic-resistant bacteria has been a major global issue for years which is facing challenges for control due to several processes and factors. Most importantly, the microbial community acts as a reservoir, and their rapid adaptive mechanisms to withstand environmental challenges are very high. As a result, long-lasting solutions for the AMR control will be a challenging issue. The resistant phenotypes will continue to occur until the establishment of a new metabolic pathway that restricts AMR acquirement and dissemination. Limiting the use of fertilizers and pesticides and controlling the effluents may reduce the ARGs in the microbial community. Replacing AMR-promoting substances in different products that causes less stress to the microbial community may limit the rise of AMR. Understanding the role of ecological factors in AMR transfer could help us devise strategies to control this fundamental evolutionary process. The most important aspect is human awareness. For this, results generated from various environmental studies should be compiled for the proper implementation of control measures.