Gut microbiota as a source of novel antimicrobials

Abstract

Bacteria, Archaea, Eukarya and viruses coexist in the human gut, and this coexistence is functionally balanced by symbiotic or antagonistic relationships. Antagonism is often characterized by the production of antimicrobials against other organisms occupying the same environmental niche. Indeed, close co-evolution in the gut has led to the development of specialized antimicrobials, which is attracting increased attention as these may serve as novel alternatives to antibiotics and thereby help to address the global problem of antimicrobial resistance. The gastrointestinal (GI) tract is especially suitable for finding novel antimicrobials due to the vast array of microbes that inhabit it, and a considerable number of antimicrobial producers of both wide and narrow spectrum have been described. In this review, we summarize some of the antimicrobial compounds that are produced by bacteria isolated from the gut environment, with a special focus on bacteriocins. We also evaluate the potential therapeutic application of these compounds to maintain homeostasis in the gut and the biocontrol of pathogenic bacteria.

Keywords: antibiotic resistance; antimicrobial; bacteriocin; biocontrol; gastrointestinal tract; homeostasis; microbiome; probiotic.

Figure 1.

Examples of assays performed to identify antimicrobial activity. (a) spot test; (b) overlay; (c) well diffusion.

Figure 2.

Examples of bacteriocin structures. (a) nisin A¹, lantibiotic; (b) microcin J25, lasso peptide; (c) microcin E-492, microcin; (d) thuricin CD subunits, sactipeptide; (e) microcin B17, linear azole or azoline containing peptides; (f) enterocin NKR-5-3C, class IIa; (g) lactococcin Q¹, class IIb; (h) lactocyclicin Q¹, class IIc; (i) lacticin Q¹, class IId; (j) colicin A¹, class III. ¹Note that these bacteriocins have not been described as of human gut origin.

Figure 3.

Examples of bacteriocin cluster organization among the different bacteriocin classes. Genes are colored according to the function of their products: red, precursor peptides; green, post-translational modifications; blue, export; yellow, immunity; pink, regulation; purple, export and immunity; orange, lysis; grey, unknown function. Class I: microcin J25; nisin A; microcin E-492; thuricin CD; microcin B17; class IIa bacteriocin 43; class IIb ABP-118; class IIc AS-48; class IId microcin S; class III colicin.