Bacteriocins and Bacteriophages: Therapeutic Weapons for Gastrointestinal Diseases?

Abstract

Bacteriocins are bactericidal peptides, ribosomally synthesized, with an inhibitory activity against diverse groups of undesirable microorganisms. Bacteriocins are produced by both gram-positive and gram-negative bacteria, and to a lesser extent by some archaea. Bacteriophages are viruses that are able to infect bacterial cells and force them to produce viral components, using a lytic or lysogenic cycle. They constitute a large community in the human gut called the phageome, the most abundant part of the gut virome. Bacteriocins and bacteriophages may have an influence on both human health and diseases, thanks to their ability to modulate the gut microbiota and regulate the competitive relationship among the different microorganisms, strains and cells living in the human intestine. In this review, we explore the role of bacteriocins and bacteriophages in the most frequent gastrointestinal diseases by dissecting their interaction with the complex environment of the human gut, analyzing a possible link with extra-intestinal diseases, and speculating on their possible therapeutic application with the end goal of promoting gut health.

Bacteriocins, Potent Antimicrobial Peptides and the Fight against Multi Drug Resistant Species: Resistance Is Futile?

“…While the treatment of cystic fibrous (CF) patients with inhaled pyocins to elevate Pseudomonas colonisation or vaginally delivered colicins to treat E. coli UTIs may offer plausible options to control these common infectious diseases. Reports indicate, however, that pyocin did not control Pseudomonas lung infections in patients with cystic fibrosis despite promising in vitro findings [42]. Specifically, the findings of Ghoul et al show a lower bacteriocin diversity correlating with the ability of P. aeruginosa to persist in infections of the CF lung coupled with several immunity systems present in this species [43].…”

“…Hertz et al report the in vitro anticancer activity of microcin E492 on colorectal and breast cancer cells at 5, 10, and 20 µg/mL via apoptosis and necrosis at concentrations of 10 and 20 µg/mL [47]. In vivo mice studies demonstrated the ability of nisin in controlling head and neck squamous cell carcinoma and oral cancer [42]. Notably, additional purified bacteriocins, including pyocin, colicin, pediocin, and microcin, have also displayed inhibitory properties against neoplastic cell lines and in xenograft mouse models [48].…”

“…Cancer cell membranes are mainly negatively charged as they contain anionic phosphatidylserine, O-glycosylated mucins, sialylated gangliosides, and heparin sulphates allowing for cancer selectivity as normal cells are neutral in charge [50]. Bacteriocins also produce an immune modulatory response against T and B cells involved in the control of cancerous pathways, stimulate cytokine secretion and modify the tumour microenvironment increasing the efficacy of cancer treatment [42].…”

Use of Prebiotics as an Alternative to Antibiotic Growth Promoters in the Poultry Industry

“…A multitude of mechanisms and functions associated with the immunomodulatory effect of prebiotics have been reported, by the activation of genes and pathways implicated in immune processes [25]. It has been cited for many authors that the use of prebiotics in poultry diets improves bird's immunity through the selective growth of beneficial microbiota, resulting in an increased production of a variety of substances, such as bacteriocins and SCFA, that, in addition to being able to inhibit growth of pathogens, play a role in signaling pathway of immune system [97][98][99]. The chicken gut microbiota, especially Lactobacillus and Bifidobacterium, has also been reported to modulate intestinal gene expression, T cell-mediated immunity, and accelerated intestinal immune system maturation, by influencing the intestinal epithelium to produce antimicrobial peptides and cytokines such as IL-12, IFN-γ, IL-10, IL-1β, and TNF-α; modulating the immune system through enhancement of phagocytosis and proliferation of immune cells such as macrophages and monocytes; enhancing production of IgA, IgM, and IgG, reactive oxygen species, and reactive nitrogen species; and proliferating natural killer cells, CD3, CD4, and CD8 T cells [25,47,75,100].…”

Toxin-mediated competition in weakly motile bacteria

“…and we have exploited the requirement a → 0 as x → ∞ as per the boundary conditions (17) in order to derive the solution (23) in x > x 0 . We choose the peak of the sech 2 -pulse in (23) to be at x = x 0 + x R /m in order to simplify subsequent calculations.…”