Anti-infection Assays for Next-generation Probiotics
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Gut Microbes as Anti-infectives
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Fecal Microbiota Transplantation
The most recent clinical guidelines for the diagnosis and treatment of C. difficile infection recommend fecal microbiota transplantation for the treatment of recurrent infection. Microbiota transplantation results in long-term remodeling of the recipient's gut microbiota to resemble that of the healthy donor. Elimination of C. difficile by restoration of healthy gut microbiota is believed to be due to several factors, including blocking of C. difficile outgrowth and direct interference with the C. difficile life cycle by metabolites like secondary bile acids and short fatty acid chains (SCFAs).
Gram-negative Escherichia coli Nissle has shown promise as a therapeutic to treat several gastrointestinal (GI) conditions. This strain can interfere with the ability of many pathogens to infect the gut, including Salmonella Typhimurium, Candida albicans, Yersinia enterocolitica, Shigella flexneri, Listeria monocytogenes, and pathogenic E. coli. Secretion of microcins and NF-κB-induced expression of the antimicrobial peptide human beta-defensin-298 are believed to be responsible for this potent anti-infection activity.
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Engineered Systems: Neutralizing Antibody Fragments
Engineered commensal microbes expressing neutralizing antibody fragments have also been pursued as therapeutic or prophylactic agents against bacterial and viral infections. Microbial therapies are attractive low-cost alternatives to traditional treatments to combat GI infections.
Fig.1 Anti-infection application of engineered commensal bacteria. (Kelly, 2020)
Probiotic Mechanism of Action Against Enteric Infections
The use of probiotics can avoid or reduce the development of different pathogens in the GI tract, either by competing for supplementation or adhesion to the GI tract area. Probiotics produce certain metabolites as they compete for supplements, for example, unstable unsaturated fats that interfere with the pH of the GI tract. A decrease in the pH of the gastrointestinal tract is detrimental to microorganisms and inhibits the growth of pathogens. Spatial adhesion competition describes the situation in which probiotics prevent pathogens from colonizing favorable locations such as intestinal villi, goblet cells, and colonial crypts.
Fig.2 Effects of metabolites of probiotics on the gut. (Iqbal, 2021)
Anti-infection Assays at Creative Biolabs
Secondary metabolites such as bacteriocins, SCFAs, indole, extracellular vesicles, and extracellular proteins are formed by probiotics. Some studies have reported that indole can inhibit the chemotaxis of pathogenic bacteria. Bacteriocins are a class of antimicrobial peptides synthesized from ribosomes. Microbes release antibacterial substances as they compete for supplements and space to reap the benefits. Antimicrobials provide immediate inhibition of specific pathogens.
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Bacterial Exclusion Properties of Probiotics
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Toxin Exclusion Properties of Probiotics
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Viral Exclusion Properties of Probiotics
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References
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Kelly, V.W.; et al. Living Therapeutics: The Next Frontier of Precision Medicine. ACS Synth Biol. 2020, 9: 3184-3201.
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Iqbal, Z.; et al. Role of probiotics in prevention and treatment of enteric infections: a comprehensive review. 3 Biotech. 2021, 11(5): 1-26.
For Research Use Only. Not intended for use in food manufacturing or medical procedures (diagnostics or therapeutics). Do Not Use in Humans.
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