Multifunctional features of lactic acid bacteria

The term lactic acid bacteria (LAB) embraces a vast number of bacterial species among which many strains have been proved to have multifunctional features including high fermentative capacity and/or important beneficial skills for humans. Within LAB, there are several phylogenetically different species belonging to the Bacilli, Clostridia, and Mollicutes classes (Garrity and Holt 2001). Within Bacilli class, six bacteria families, i.e. Aerococcaceae, Carnobacteriaceae, Enterobacteriaceae, Lactobacillaceae, Leuconostocaceae, and Streptococcaceae, encompass the LAB genera mainly associated with food such as Lactococcus, Enterococcus, Streptococcus, Leuconostoc, Weissella, Oenococcus, Pediococcus, Tetragenococcus, and Carnobacterium (Franz, and Holzapfel 2011).

LAB share the characteristic to be Gram-positive, usually non-motile and non-spore forming, catalase-negative, aerotolerant organisms, forming lactic acid as the main fermentative product through carbohydrates degradative metabolism (Axelsson 2004). The ability to ferment sugar, the increase of the acidity, and the production of several secondary metabolites are the main reason why LAB, since ancient times, have been used as a sort of starter cultures in order to improve the preservation, flavor, and texture of fermented food and feed products (Kleerebezem et al. 2017; Petruzzi et al. 2017; Kumar et al. 2017; Jeon et al. 2015). Furthermore, LAB are also exploited to increase the nutritional value of fermented foods, e.g., in yogurt, profiting by their ability to produce essential substances such as folate and riboflavin (Da Silva et al. 2016).

Several LAB strains, most of them belonging to Lactobacillus genus, have been shown to perform human and animal health-promoting activities, such as modulation of immune response, prevention of cancer, reduction of chronic bowel inflammations and cholesterol levels, improvement of the intestinal barrier, inhibition of pathogenic organisms, beneficial interactions with the endogenous intestinal microbiota (Mombelli and Gismondo 2000; Pothuraju and Sharma 2018; Vijayaram and Kannan 2018). The claim by which these microorganisms are commonly known is the term “probiotics” defined as “live microorganisms which when administered in adequate amount confer a health benefit on the host” (FAO/WHO 2001).

In order to absolve to probiotic features, beneficial microorganisms need to tolerate the harsh conditions of the oro-gastro-intestinal environment, adhere on the intestinal mucosa and colonize the gut tract, and produce helpful bioactive molecules (Arena et al. 2017; Al-Tawaha and Meng 2018). The criteria by which microorganisms can be claimed probiotics are listed in Table 1, although they do not need to possess all cited properties but only some specific features, according to the aim to be reached.

Table 1 Principal criteria by which microorganisms can be claimed as probiotics
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In this review, we tread the current state of the art on the antiviral and antifungal ability of lactic acid bacteria that hold probiotic skills.

Probiosis and immunobiosis

Probiotic LAB have been introduced widely in human and animal feed in increasing manner in the past last decades due to their positive impact on the prevention of some diseases and the maintaining of a well state of health. There is an active molecular dialog between the commensal microorganisms and the host mucosal immune system (Galdeano et al. 2007). In humans, probiotics can interact with the gut-associated lymphoid tissue (GALT) and modulate the immune response to injury and pathogenic organisms. Peyer’s patches, i.e. lymphoid follicles located in the submucosa layer of the ileum and intestinal mucosa layer, are involved in the intestinal immune defense recognizing antigens and pathogenic microorganisms through specialized cells called microfold cells (M cells). Peyer’s patches hold macrophages, dendritic cells, B lymphocytes, and T lymphocytes that actively contrast the possible enemies (Bonnardel et al. 2015; Diener 2016). The intestinal IgA cells are mainly produced in the Peyer’s patches and their principal role is to protect the digestive tract which constitutes a border line between the external and the internal environments. They continually select what is useful for the organism, such as food nutrients, and what is harmful, such as pathogenic microorganisms and viruses (Laissue et al. 1993). Probiotic bacteria, such as strains of Lactobacillus casei and Bifidobacterium breve, have been recently reported to enhance the levels of specific IgA contributing to improve the mucosal resistance against Candida infections (Mendonça et al. 2012).

Several studies tried to outline the mechanisms through which probiotic bacteria can have an influence in the stimulation of immune system. Plausibly, the cell wall of probiotics seems to promote the macrophages activation and the augmentation of IgA-producing cells in the gut lamina propria. Probiotic cells may be able to bind M cells and/or to direct the macromolecular antigen uptake to Peyer’s patches (Majamaa et al. 1995; Isolauri 1999). Thus, specific components of the probiotic cell are essential for the immune modulation and, earlier, for adhesion ability to intestinal mucosa, which is indispensable in order to create an intimate contact between bacteria and the intestine (Santarmaki et al. 2017). There are many evidences that probiotic bacteria producing vitamins could provide anti-inflammatory effects that could be considered as adjunct IBD treatments to decrease some of the unwanted side effects caused by primary treatments (de Moreno de LeBlanc et al. 2018).

Some LAB, such as Lactobacillus rhamnosus and Lactobacillus reuteri, have been demonstrated to raise the level of IgA-specific antigen-secreting cells to rotavirus and reduce the shedding of rotavirus (Majamaa et al. 1995). Albeit the underlying mechanisms are not well elucidated, the adhesion ability of the aforementioned probiotic species would seem to be the key for the reduction of diarrhea caused by rotavirus (Shornikova et al. 1997; Tuomola et al. 1999), accompanied by the capability to stimulate antibodies against rotavirus (O’Halloran et al. 1998).

In parallel to adhesion, co-aggregation is a suitable feature preferable associate to a probiotic strain. Co-aggregation is the ability of microorganisms to adhere to each other, such as probiotic-probiotic and/or probiotic-pathogen. The co-aggregation properties of probiotic bacteria isolated from food products, such as some strains of Lactobacillus acidophilus, Lactobacillus plantarum, L. rhamnosus, Lactobacillus paracasei, and L. reuteri, were demonstrated to be specific and time-dependent against Escherichia coli and the oral pathogen Streptococcus mutans, underlying the possible anti-caries properties of probiotic (Twetman et al. 2009; Prabhurajeshwar and Chandrakanth 2017).

Thanks to the intimate contact occurring upon co-aggregation, probiotics can inhibit the harmful microorganisms by producing antimicrobial molecules in very close proximity of them. The antimicrobial substances mainly produced by LAB can be classified into low and high molecular mass compounds (i.e., with a molecular mass < 1000 Da and > 1000 Da, respectively) (Šušković et al. 2010). The first group, also named non-bacteriocin group, includes organic acids (such as lactic, acetic, phenyllactic, 4-hydroxyphenyllactic, benzoic acids) (Sjögren et al. 2003; Valerio et al. 2004; Niku-Paavola et al. 1999), hydrogen peroxide, diacetyl, acetaldehyde, acetoin, and carbon dioxide. In the undissociated form, organic acids can diffuse across the cell membrane exploiting the chemical gradient caused by the different pH between the cytosol (alkaline) and the external environment (acidic). Once inside the bacteria cell, they can interfere with metabolic functions and dissipate the membrane potential (Tejero-Sariñena et al. 2012; Lorca and de Valdez 2009). Hydrogen peroxide, instead, is able to alter the redox potential of bacterial cell and to damage the protein structures due to its oxidizing effect (Pridmore et al. 2008; Reid 2008). Diacetyl, acetaldehyde, and acetoin, produced through heterofermentative metabolisms, play a role in the enhancement of shelf life of some foods as they can control the growth of spoilage microorganisms (Jyoti et al. 2003; Lanciotti et al. 2003). Carbon dioxide is responsible for the inhibition of enzymatic decarboxylations and the dysfunction of membrane permeability in fungi.

The second group of antimicrobial compounds produced by LAB, i.e., high molecular mass substances, includes proteinaceous molecules referred to as bacteriocins (Sidooski et al. 2018). The bacteriocins produced by LAB are classified based on their molecular weight, heat sensitivity, mechanism of action, and spectrum of activity (review by Šušković et al. 2010; López-Cuellar et al. 2016; Collins et al. 2017). Regardless of the type of bacteriocins (e.g., heat-stable or heat-labile, single or two-peptide bacteriocin, linear or circular structure), these molecules have received considerable attention due to their potential application in food industry as biopreservatives. Besides, the bacteriocin biosynthetic ability is a desirable probiotic feature, as their antibacterial spectrum can embrace spoilage organisms and foodborne pathogens (Chen and Hoover 2003). For LAB bacteriocins, four classes have been proposed: (i) lantibiotic bacteriocins, (ii) non-lantibiotic bacteriocins, (iii) bacteriolysins, and (iv) lipid- or carbohydrate-required bacteriocins (Šušković et al. 2010). The mode of action of bacteriocins can vary from the modulation of enzyme activity, inhibition of outgrowth of spores, destabilization of cell membrane, or formation of pores, which can occur through binding lipids, dissipating proton motive force, thus altering the chemical membrane potential (Chen and Hoover 2003; Héchard and Sahl 2002; Venema et al. 1995; Cotter et al. 2005).

Biopreservative activity of probiotic LAB: from bacteriocins to organic acids through an in situ fermentation approach

In the food fermentation field, those cultures of microorganisms, properly selected and added to raw material in order to accelerate and steer the fermentation process, are named starter cultures. Many LAB are commonly used as microbial starters in several fermented foods based on matrices such as vegetables, meat, cereals, and milk (Sandine and Thunell 2018; Russo et al. 2016). In these products, the starter microorganisms, besides contributing to transform the raw material into a more palatable product, synthesize several metabolites, such as lactic acid, acetic acid, hydrogen peroxide, diacetyl, bacteriocins, which act as natural preserving agents. Thus, a greater acidifying capacity and/or the ability to produce larger amounts of bacteriocins are among the criteria by which the starter bacteria are selected.

Bacteriocin-producing starter cultures may not only contribute to food safety, by inhibiting foodborne pathogen microorganisms, but also prevent the growth of undesirable autochthonous bacteria that produce off-flavor. Some LAB cultures can be particularly capable to produce antimicrobial compounds but may be unable to satisfactorily carry out the desired fermentation of that particular food product. These cultures could be added during or after the fermentation process only for increasing the shelf life of the food product. These bacteriocin-producing adjunct cultures need to be also opportunely selected in order to not interfere with the performances of starter cultures and negatively affect the fermentation process (Bravo et al. 2009; Silva et al. 2018; O’Sullivan et al. 2003). Bacteriocins-producing LAB can be also added to non-fermented products, with the aim to protect them during their shelf life. In these cases, the used cultures are named bacteriocin-producing protective bacteria and they are added as food ingredient in food manufacturing (Woraprayote et al. 2016). Many studies have been carried out to improve the biopreservative action of microbes during the conservation process of the food product. Thus, numerous researches aimed to develop immobilization or microencapsulation methods for bacteriocin-producing bacteria or purified bacteriocins, directly into the food matrix, or on its surface, or in the food packaging (Champagne and Fustier 2007; Woraprayote et al. 2016; Woraprayote et al. 2018; Malhotra et al. 2015).

Bacteriocins used in combination with other methods of preservation, such as chemical additives (e.g., EDTA, sodium lactate, and potassium diacetate), heating, and high-pressure treatments, have been shown to improve the biopreservative action (Egan et al. 2016). To date, nisin (Nisaplin, Danisco; licensed as a food preservative (E234)) and pediocin PA1 (MicrogardTM, ALTA 2431, Quest) are the only bacteriocins commercialized as food preservatives (Simha et al. 2012; Favaro et al. 2015). However, the screening and characterization of numerous other bacteriocins produced by LAB could expand the industrial application of these compounds in the near future (Sánchez-Hidalgo et al. 2011; Suda et al. 2012).

Nisin, produced principally by Lactococcus lactis but also by Streptococcus strains (O’Connor et al. 2015), is mainly active against Gram-positive bacteria, e.g., Listeria and Staphylococcus genera, and the spore forming bacteria, e.g., Bacillus and Clostridium genera (Chen and Hoover 2003). Pediocin is produced by Pediococcus spp. and is highly active against L. monocytogenes and S. aureus pathogens, and also against Pseudomonas genera and E. coli species (Garsa et al. 2014).

Overall, the antifungal activity of LAB appears to be correlated to metabolic products that can also act in synergy. The chemical nature and the produced amount of these compounds are species- and strain-dependent (Crowley et al. 2013) and include organic acids (hydrocinnamic acid, dl-phenyllactic acid, dl-hydroxyphenyllactic acid, polyporic acid, azelaic acid, 2-hydroxybenzoic acid, 4-hydroxybenzoic acid, p-coumaric acid, vanillic acid, caffeic acid, succinic acid, 2-pyrrolidone-5-carboxylic acid), fatty acids (decanoic acid, 3-hydroxydecanoic acid, (S)-(-)-2–hydroxyisocaproic acid, coriolic acid, ricinoleic acid), cyclopeptides [cyclo(l-Pro-l-Pro), cyclo(l-Leu-l-Pro), cyclo(l-Tyr-l-Pro), cyclo(l-Met-l-Pro), cyclo(Phe-Pro), cyclo(Phe-OH-Pro), cyclo(l-Phe-l-Pro), cyclo(l-Phe-trans-4-OH-l-Pro), cyclo(l-His-l-Pro), and cyclo(Leu-Leu)], reuterin, hydrogen peroxide, and volatile compounds such as diacetyl (Leyva Salas et al. 2017).

In the overview to focus on the antifungal and antiviral activity of LAB, an example of the use of bacteria to prevent and/or decelerate the fungal growth in food could be that of cereal-based fermented products. Cereals and their derivative products are sensitive to the contamination by spoilage filamentous fungi, and this is a critical problem both from an economic point of view, due to the loss of raw material, and from a safety concern, due to the potential production of mycotoxins into food matrix (Pitt and Hocking 2009; Oliveira et al. 2014). LAB can have antagonistic activity against filamentous fungi, and, although the real mechanisms by which they contrast the fungal development are still unclear, it seems associated to cytoplasmic acidification and failure of proton motive forces (Reis et al. 2012; Russo et al. 2017). Among organic acids, phenyllactic acid (PLA) seems to be the most antifungal compound produced by LAB (Lavermicocca et al. 2000; Ström et al. 2002; Cortés-Zavaleta et al. 2014). Consequently, the addition of LAB cultures, or their cell free supernatants, showing antifungal activity, has been proposed for several food industry applications, including dairy and cereal-based productions, malting process, and fruits and vegetables storage (Axel et al. 2015; Oliveira et al. 2015; Cheong et al. 2014; Crowley et al. 2012; Russo et al. 2017). In malting wheat grains, treatments with strains of Lactobacillus sakei, Pediococcus acidilactici, and Pediococcus pentosaceus have been shown to reduce the production of Fusarium mycotoxins and the development of F. culmorum and F. poae. That reduction was linked to probable mechanisms of binding of mycotoxins b and/or their detoxification by LAB (Juodeikiene et al. 2018). In fact, it seems plausible that LAB could detain enzymes able to destabilize the mycotoxin structure making them less active. This feature has been already reported for other microorganisms, including Eubacterium, which are able to produce specific enzymes (e.g., deepoxidase) that catalyze the oxidation of the toxic epoxy ring of some mycotoxins in a strain-specific manner (Karlovsky 1999; Garvey et al. 2008; Juodeikiene et al. 2012; Mccormick 2013; Hathout and Aly 2014).

Recently, Miezkin et al. (2017) found a synergist effect of acetic, lactic, 2-pyrrolidone-5-carboxylic, (S)-(-)-2–hydroxyisocaproic, and 2-hydroxybenzoic acids produced by Lactobacillus harbinensis strains against several fungi. Moreover, the production of diacetyl together with 2,3-pentadione, acetic acid, and butanoic acid was suggested as the key antifungal capability of L. paracasei strain (Aunsbjerg et al. 2015).

In Fig. 1, a schematic representation of probiosis, immunobiosis, and biopreservative activity of LAB is reported.

Fig. 1
figure 1

Schematic representation of probiosis, immunobiosis, and biopreservative activity of lactic acid bacteria (LAB)

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Probiosis and antiviral activity

In recent years, the problem of antibiotic resistance has troubled both the scientific community and consumers. Antibiotic resistance of pathogenic bacteria is the mechanism through which bacteria become resistant to the antibiotic used in the medical treatments of the diseases. The overuse of those medications, as well as a lack of new drug development by the pharmaceutical industry, determined the worldwide emergence of resistant bacteria (Ventola 2015). Consequently, many efforts have been made in order to find antibiotic bio-alternatives, such as phages, bacteriocins, essential oils, metals, minerals, organic acids, or enhancement of modulation of human immune response (Lazarus et al. 2018; Ouwehand et al. 2016). In this regard, probiotics have been found to reduce the risk of certain infectious disease directly acting against the etiologic agent of the disease or indirectly modulating the host’s immune response and modifying the gut microflora in order to prevent pathogen colonization (Cavera et al. 2015).

The multiple actions of probiotic in the oro-gastrointestinal tract include the production of metabolites that modify the acid and redox environment and disadvantage the pathogenic colonization, the enhancement of intestinal barrier function and mucin production, and the competition for nutrients and adhesion sites against pathogens. Moreover, the production of antimicrobial compounds that directly intervene to reduce the growth of enemies and the stimulation of immune system response are two main mechanisms able to contrast the onset of infections and diseases (Arqués et al. 2015; Arena et al. 2016, 2014; Yahfoufi et al. 2018). The consumption of probiotic microorganisms, such as Lactobacillus johnsonii and B. lactis, has been related to increased phagocytosis of pathogens, such as E. coli (Schiffrin et al. 1994). Other probiotic bacteria have been shown to activate the lymphoid cells of the gut-associated lymphoid tissue through bacterial cell envelope constituents, such as peptidoglycan, and thanks to the intimated contact that is established when the probiotic cell adheres to the intestinal monolayer surface (Ranadheera et al. 2014). However, probiotics could also modulate immune response by acting on the permeability of the intestine to eventual antigens and enemies, including viruses, and by producing antimicrobial metabolites (Seo et al. 2010).

LAB can exert antiviral capabilities by three main mechanisms: (i) the direct interaction with viruses, (ii) the production of antiviral inhibitory substances, or/and (iii) the stimulation of immune system. The direct interaction is probably the most common process by which probiotic bacteria are able to inactive viruses. It occurs through adsorption or trapping the virus and is strictly a strain-dependent mechanism (Al Kassaa et al. 2014). Strains of L. paracasei, L. rhamnosus, L. plantarum, and L. reuteri have been studied for their ability to trap vesicular stomatitis virus (VSV) (Botić et al. 2007), while Enterococcus faecium and Lactobacillus gasseri strains have been reported to directly inactive influenza viruses and herpes simplex type 2 (HSV-2), respectively (Al Kassaa et al. 2015; Wang et al. 2013). Frequently, many probiotics can attach to cell surfaces, thereby affecting the first stages of the viral infection by blocking the virus binding to the cell receptors and reducing its entrance into the cell (Bermudez-Brito et al. 2012; Varyukhina et al. 2012).

Moreover, antiviral activity by probiotic can occur also through the stimulation of host’s immune system. A strain of Bifidobacterium adolescentis has been proved to decrease HPV16 mRNA transcript and protein levels demonstrating antiviral capability (Cha et al. 2012). As the HPV oncogene mRNA and protein overexpression are correlated to carcinogenesis process of the cervical cancer (Woodman et al. 2001), the downregulation exerted by B. adolescentis highlights the potential application of that strain in the prevention of HPV-associated cervical cancer (Cha et al. 2012; Li et al. 2010).

The production of inhibitory substances can also contrast viruses and their activities. For example, hydrogen peroxide produced by LAB is able to attenuate human immunodeficiency virus (Conti et al. 2009), while lactic acid, the main product of the LAB metabolism, reduce the pH values and make the environment unfavorable for viruses, such as human lymphotropic virus and herpes simplex virus (Martin et al. 1985, 2010; Tuyama et al. 2006). Other bacterial molecules, such as non-protein cell wall component, could contrast viral replication (Mastromarino et al. 2011). Several LAB bacteriocins have been investigated for their ability to reduce coliphage HSA viral progeny (Humaira et al. 2006) or to affect intracellular viral multiplication and late stages of replication of herpes simplex virus (HSV-1 and HSV-2) (Wachsman et al. 1999, 2003; Todorov et al. 2005). The antiviral effect of bacteriocins during viral multiplication seems to depend on their ability to avoid the aggregation of viral particles by blocking the receptors sites on host cells (Wachsman et al. 2003). Numerous studies on antiviral activity against viral respiratory infections brought to light that the oral administration of probiotic LAB, such as strains of L. plantarum, Lactobacillus casei, and Lactobacillus fermentum, decreased influenza virus effects (Maeda et al. 2009; Boge et al. 2009; Olivares et al. 2007). Moreover, a strain of L. rhamnosus, in combination with B. animalis subsp. lactis biotype, has been proved to ameliorate the incidence of respiratory virus infections (RVI) (Rautava et al. 2009). The ability to beneficially modulate the IFN-c and IL secretion in order to contrast respiratory syncytial virus was correlated to the assumption of L. rhamnosus (Chiba et al. 2013; Salva et al. 2011). L. plantarum was investigated for its antiviral and protective effects against influenza virus, associated to a beneficial modulation of innate immunity of dendritic and macrophage cells and cytokines production pattern. The strains were able to modulate the levels of cytokines IL-12 and IFN-c in bronchoalveolar lavage fluids, and to reduce the degree of inflammation upon infection with influenza virus (Park et al. 2013).

The most known and studied antiviral activity by LAB is that against enteric viruses that are commonly associated with diarrhea and gastroenteritis in humans (Maragkoudakis et al. 2010). L. casei and L. rhamnosus stains could reduce the symptoms of acute infectious diarrhea in infants and children (Agarwal and Bhasin 2002; Szajewska and Mrukowicz 2001). The production of NO− and H2O2 by strains of E. faecium, L. fermentum, Lactobacillus pentosus, and L. plantarum could account for their antiviral activity (Al Kassaa et al. 2014).

The research focused on sexually transmitted viruses (STV) that are relatively more recent and various inhibitory activities have been found against widespread viruses such as human papilloma (HPV) and human immunodeficiency virus (HIV) (Weiss et al. 2004). Some authors have shown that the probiotic activity against these kinds of virus possibly involves the suppression of oncogene proteins (Cha et al. 2012) and/or the stimulation of macrophages activity (Khania et al. 2012).

Several studies proposed an antiviral mechanism based on probiotic metabolites that can alter the production of viral proteins. In detail, Olaya Galán et al. (2016) suggested that four metabolites produced by probiotic bacteria were able to reduce the quantity of the intracellular NSP4 protein, which is produced by rotavirus during the infection. The consumption of probiotics has been associated also to an amelioration of the incidence of viral respiratory infection such as those caused by rhinovirus. The ingestion of Bifidobacterium animalis subspecies lactis has been shown to have an effect on the baseline state of innate immunity in the nose and on the subsequent response of the human host to rhinovirus infection in a clinical trial of volunteers. B. animalis subspecies lactis seems to manifest its anti-rhinovirus activity by modulating the inflammatory host response, e.g., CXCL8 nasal response, and by decreasing the shedding of virus in the nasal secretion (Turner et al. 2017).

Several compounds produced by probiotic microorganisms have been associated with antiviral activity. For example, cells from two L. plantarum strains, as well as their derivatives, were found to antagonize the enterovirus Coxsackievirus B4 (CV-B4), which can infect different human tissues and provoke abnormal function or destruction of various organs and cells (Arena et al. 2018). The inhibitory effect by L. plantarum against CV-B4 was associated to a direct interaction probiotic-pathogen, although the antiviral mode of action needs to be further elucidated. Similarly, other authors described antiviral effect by L. reuteri against enteroviruses Coxsackievirus A and Enterovirus 71, achieved through a direct physical interaction between bacterial and viral particles, which hinders the virus entry into host cells (Ang et al. 2016). Moreover, another study showed that a B. adolescentis strain was active against Coxsackievirus B3 (CV-B3) by inhibiting its intracellular replication and acting on host IFN-mediated antiviral response (Kim et al. 2014).

Probiotics could be also a suitable alternative or co-treatment of urogenital infections with the aim to reduce antibiotic use and avoid the increasing development of resistance. In women, in most of the studies, probiotic intervention was supplied via vaginal route although also the oral via seems to be effective. In the vaginal mucosa environment, probiotic colonization determines a pH reduction and, then, an inhibition of bacterial vaginosis, urinary tract infections, vulvovaginal candidiasis, and human papillomavirus (HPV) (Hanson et al. 2016). The use of probiotic L. rhamnosus GG has been demonstrated to be efficient in the prevention of mucosal infections by the fungal pathogen Candida albicans, probably due to a reduction of its adhesion, invasion, and hyphal extension in vaginal and oral sites (Mailänder-Sánchez et al. 2017).

Conclusion

LAB represent a remarkable resource in the fight against fungi and viruses and key allies allowing the potential reduction of fungicidal and virucidal chemical agents. Such microorganisms are able both to act directly against pathogens and through the production of metabolites that interfere with fungi and virus activity. Although the detailed mechanisms by which LAB contrast microbial enemies are not well elucidated, many steps forward have been made in the last decades and many others are still being done, as nowadays, the attention of consumers and scientists is oriented toward an increasing use of bio-renewable and non-chemical approaches in both food manufacture and medical treatments.