In silico identification of bacteriocin gene clusters in the gastrointestinal tract, based on the Human Microbiome Project’s reference genome database

Abstract

BackgroundThe human gut microbiota comprises approximately 100 trillion microbial cells which significantly impact many aspects of human physiology - including metabolism, nutrient absorption and immune function. Disturbances in this population have been implicated in many conditions and diseases, including obesity, type-2 diabetes and inflammatory bowel disease. This suggests that targeted manipulation or shaping of the gut microbiota, by bacteriocins and other antimicrobials, has potential as a therapeutic tool for the prevention or treatment of these conditions. With this in mind, several studies have used traditional culture-dependent approaches to successfully identify bacteriocin-producers from the mammalian gut. In silico-based approaches to identify novel gene clusters are now also being utilised to take advantage of the vast amount of data currently being generated by next generation sequencing technologies. In this study, we employed an in silico screening approach to mine potential bacteriocin clusters in genome-sequenced isolates from the gastrointestinal tract (GIT). More specifically, the bacteriocin genome-mining tool BAGEL3 was used to identify potential bacteriocin producers in the genomes of the GIT subset of the Human Microbiome Project’s reference genome database. Each of the identified gene clusters were manually annotated and potential bacteriocin-associated genes were evaluated.ResultsWe identified 74 clusters of note from 59 unique members of the Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria and Synergistetes. The most commonly identified class of bacteriocin was the >10 kDa class, formerly known as bacteriolysins, followed by lantibiotics and sactipeptides.ConclusionsMultiple bacteriocin gene clusters were identified in a dataset representative of the human gut microbiota. Interestingly, many of these were associated with species and genera which are not typically associated with bacteriocin production.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-015-0515-4) contains supplementary material, which is available to authorized users.

Discovery of a novel lantibiotic nisin O from Blautia obeum A2-162, isolated from the human gastrointestinal tract

“…An in silico study of the genomes of gut bacteria from the Human Microbiome Project identified lantibiotic-associated genes from a range of genera, including R. obeum A2-162 [33]. Other Clostridiales have been shown to produce the bacteriocins albusin B, a type III bacteriocin [57], and the lantibiotics ruminococcin A and ruminococcin C [58,59], but these were not found to have any sequence similarities to the nisin O cluster.…”

“…It is a rich potential source of novel antimicrobials that have evolved to function in the challenging conditions of the gastrointestinal tract, and recent research suggests that bacteriocin production is widespread [32,33]. Using genome mining of human gut bacteria, new lantibiotic sequences sharing considerable amino acid sequence homology with class AI lantibiotics, and especially nisin U, were discovered from anaerobic bacterium Blautia obeum A2-162.…”

Microbiome therapeutics — Advances and challenges

“…A producer cell encodes both toxic and immunity functions, killing neighbouring cells while protecting itself and its progeny from the effects of the bacteriocin. Recent studies have used metagenomics to identify bacteriocins [103,104], shown potential fitness advantages of producers in vivo [105], and observed protective effects of producers against pathogens [106,107]. As these molecules seem to play a role in modulating microbial populations within a host, they may prove useful tools for subtractive-type therapies.…”

Drug Targeting of the Human Microbiome

“…The bacteriocin pyocin S5 from P. aeruginosa PAO1 has been engineered to eradicate Pseudomonas species phylogenetically close to PAO1 [66], and hence is a prospective therapeutic for treating Pseudomonas infections. Recently, many bacteriocins have been identified from the gut microbiota [67,68]. For example, thuricin CD, which has a narrow spectrum, is effective in killing C. difficile without significant impact on the microbiota composition in a distal colon model [69], while the bacteriocin Abp118 produced in Lactobacillus salivarius UCC118 is found to be directly responsible for significantly protecting mice against Listeria monocytogenes infection [70].…”