Live Biotherapeutics Drug Discovery Service for Bacterial Infections

Overview

As a probiotic, Lactobacillus is emerging as a powerful weapon to block pathogen adhesion, and biofilm formation, and control pathogen overgrowth. Therefore, the use of probiotics or their metabolites to block bacterial communication and aggregation and interfere with biofilm formation and stability may represent a new frontier in clinical microbiology and an effective alternative to antibiotic therapy. Lactic acid bacteria are beneficial bacteria that have shown significant utility in the prevention and treatment of intestinal, oral, and urinary tract infections. They protect the host by different mechanisms, such as lowering pH, producing antimicrobial agents, providing competitive exclusion of pathogens, and reducing excessive inflammation. Probiotics have potential applications in the treatment of infectious diseases due to their ability to interfere with pathogen growth, quorum sensing, and biofilm formation. Probiotics protect the gut from infection by preventing the adhesion of pathogens. Probiotics can also combat biofilm formation by pathogenic E. coli. However, their effectiveness in blocking the formation of pathogenic bacteria and fungal biofilms is based on probiotic combinations. Probiotics also produce bioactive components (e.g., extracellular polysaccharides, enzymes, cell wall debris, antimicrobial peptides, and several other bioactive molecules) that exert antimicrobial properties.

Probiotics Mechanisms Against Pathogens

The mechanisms of action of probiotics against enteric pathogens are diverse, heterogeneous, and probably strain-specific. Several studies have described the antimicrobial activity of various probiotic strains, AMPs, and other antimicrobial molecules produced by these strains capable of inhibiting bacterial growth, disrupting biofilm formation, or interfering with quorum sensing, most of which have been used in vitro models. Commensal bacteria can also act as a protective barrier against pathogens by providing mucosal protection and stimulating the immune system. Secondary metabolites and peptides with antimicrobial activity secreted by some probiotic strains may also interact directly with the host or pathogen.

Fig.1 Probiotic mechanisms of action against enteric pathogens in the GIT. (Van,2020)Fig.1 Probiotic mechanisms of action against enteric pathogens in the GIT.1

Production of Antimicrobial Compounds

Antimicrobial compounds produced by probiotics can exert direct antimicrobial effects against competing intestinal pathogens, thereby potentially preventing pathogenic colonization of the GI tract.

  • Bacteriocins

Bacteriocins may have bacteriostatic or direct bactericidal effects on pathogens, thereby limiting the ability of cells to colonize the gut. Bacteriocins produced by probiotics are a key mechanism of action in GIT for pathogen inhibition.

  • Bacteriocin-like Inhibitory Substances

Bacteriocin-like inhibitory substances (BLIS) have a broader spectrum of antimicrobial activity.

  • Organic Acids

Probiotics and commensal bacteria fermentor the carbohydrates in GIT to produce metabolites such as acetic acid, formic acid, succinic acid, and lactic acid, which make the intestinal environment acidic and inhibit the growth of bacterial pathogens.

  • Hydrogen Peroxide

Hydrogen peroxide production by commensal or probiotic bacteria may also be an important antibacterial mechanism.

  • Biosurfactants

Several lactic acid bacteria strains have been isolated that produce cell-bound or secreted biosurfactants with antibacterial, antiviral, and antifungal properties.

Engineering Probiotics for the Treatment of Bacterial Infections

In recent years, engineered probiotics have attracted much attention to inhibit pathogenic bacteria to maintain gastrointestinal health and treat bacterial infections. According to this mechanism, a variety of probiotics have been developed, most of which have shown good specificity and inhibitory effects against pathogens. Inhibition of biofilm formation by engineered probiotics is one of the antibacterial mechanisms. An E. coli Nissle 1917 with both a micromycin H47 production system and a tetrathionate sensing system was developed to inhibit Salmonella infection.

Fig.2 Engineering probiotic strain for the inhibition of Salmonella infection. (Zhou, 2020)Fig.2 Engineering probiotic strain for the inhibition of Salmonella infection.2

If you are developing probiotic therapy to treat bacterial infections, you may be interested in our services. Creative Biolabs can provide probiotic strain products, as well as antimicrobial testing and development of engineered therapeutic strain services. Please contact our expert team today for more details.

References

  1. Van Zyl, Winschau F., Shelly M. Deane, and Leon MT Dicks. "Molecular insights into probiotic mechanisms of action employed against intestinal pathogenic bacteria." Gut microbes 12.1 (2020): 1831339.
  2. Zhou, Zhao, et al. "Engineering probiotics as living diagnostics and therapeutics for improving human health." Microbial Cell Factories 19 (2020): 1-12.

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