Ruminococcin C, a new anti-Clostridium perfringens bacteriocin produced in the gut by the commensal bacterium Ruminococcus gnavus E1

Crost, Emmanuelle H.; Ajandouz, El Hassan; Villard, Claude; Geraert, P. A.; Puigserver, Antoine; Fons, Michel

doi:10.1016/j.biochi.2011.05.001

Cited by 49 publications

(42 citation statements)

References 33 publications

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“…Although preliminary studies to study the biological effects of target molecules have been carried out for three microbiota-derived RiPPs (139–143), their biological relevance have not yet been tested experimentally. Although colonization studies in gem-free mice have the advantage of simplicity, there are drawbacks: (i) a molecule derived from a mono-colonist could be produced at super-physiological levels, leading to a false signal; (ii) the activity of some molecules, e.g., immune modulators, may require the activity of co-stimulatory signals from other bacterial species; and (iii) the biological relevance of certain molecules, e.g.…”

Section: Discussionmentioning

confidence: 99%

Small molecules from the human microbiota

Donia

Fischbach

2015

Science

611

518

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Developments in the use of genomics to guide natural product discovery and a recent emphasis on understanding the molecular mechanisms of microbiota-host interactions have converged on the discovery of natural products from the human microbiome. Here, we review what is known about small molecules produced by the human microbiota. Numerous molecules representing each of the major metabolite classes have been found that have a variety of biological activities, including immune modulation and antibiosis. We discuss technologies that will affect how microbiota-derived molecules are discovered in the future, and consider the challenges inherent in finding specific molecules that are critical for driving microbe-host and microbe-microbe interactions and their biological relevance.

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Section: Discussionmentioning

confidence: 99%

Small molecules from the human microbiota

Donia

Fischbach

2015

Science

611

518

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“…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. The discrepancy between the GC content of the structural gene region, the remaining cluster and the producer organism, and the presence of transposase-like sequences at the 3¢ end of the cluster could signify that some ORFs have been acquired by horizontal gene transfer.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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A novel lanC-like sequence was identified from the dominant human gut bacterium Blautia obeum strain A2-162. This sequence was extended to reveal a putative lantibiotic operon with biosynthetic and transport genes, two sets of regulatory genes, immunity genes, three identical copies of a nisin-like lanA gene with an unusual leader peptide, and a fourth putative lanA gene. Comparison with other nisin clusters showed that the closest relationship was to nisin U. B. obeum A2-162 demonstrated antimicrobial activity against Clostridium perfringens when grown on solid medium in the presence of trypsin. Fusions of predicted nsoA structural sequences with the nisin A leader were expressed in Lactococcus lactis containing the nisin A operon without nisA. Expression of the nisA leader sequence fused to the predicted structural nsoA1 produced a growth defect in L. lactis that was dependent upon the presence of biosynthetic genes, but failed to produce antimicrobial activity. Insertion of the nso cluster into L. lactis MG1614 gave an increased immunity to nisin A, but this was not replicated by the expression of nsoI. Nisin A induction of L. lactis containing the nso cluster and nisRK genes allowed detection of the NsoA1 pre-peptide by Western hybridization. When this heterologous producer was grown with nisin induction on solid medium, antimicrobial activity was demonstrated in the presence of trypsin against C. perfringens, Clostridium difficile and L. lactis. This research adds to evidence that lantibiotic production may be an important trait of gut bacteria and could lead to the development of novel treatments for intestinal diseases.

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“…Fisher axenic rats came from the ANAXEM platform (INRA, Jouy-en-Josas, France) and were reared as previously described (15). Three Fisher axenic rats were inoculated with around 10 9 cells of the E1 strain (0.5 ml of fresh culture) by the intragastric route.…”

Section: (Lbg) Guar Gum (Gg) Para-nitrophenyl-␣-d-galactopyranosidementioning

confidence: 99%

Functional Analysis of Family GH36 α-Galactosidases from Ruminococcus gnavus E1: Insights into the Metabolism of a Plant Oligosaccharide by a Human Gut Symbiont

Cervera-Tison

Tailford

Fuell

et al. 2012

Appl Environ Microbiol

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dRuminococcus gnavus belongs to the 57 most common species present in 90% of individuals. Previously, we identified an ␣-galactosidase (Aga1) belonging to glycoside hydrolase (GH) family 36 from R. gnavus E1 (M. Aguilera, H. Rakotoarivonina, A. Brutus, T. Giardina, G. Simon, and M. Fons, Res. Microbiol. 163:14 -21, 2012). Here, we identified a novel GH36-encoding gene from the same strain and termed it aga2. Although aga1 showed a very simple genetic organization, aga2 is part of an operon of unique structure, including genes putatively encoding a regulator, a GH13, two phosphotransferase system (PTS) sequences, and a GH32, probably involved in extracellular and intracellular sucrose assimilation. The 727-amino-acid (aa) deduced Aga2 protein shares approximately 45% identity with Aga1. Both Aga1 and Aga2 expressed in Escherichia coli showed strict specificity for ␣-linked galactose. Both enzymes were active on natural substrates such as melibiose, raffinose, and stachyose. Aga1 and Aga2 occurred as homotetramers in solution, as shown by analytical ultracentrifugation. Modeling of Aga1 and Aga2 identified key amino acids which may be involved in substrate specificity and stabilization of the ␣-linked galactoside substrates within the active site. Furthermore, Aga1 and Aga2 were both able to perform transglycosylation reactions with ␣-(1,6) regioselectivity, leading to the formation of product structures up to [Hex] 12 and [Hex] 8 , respectively. We suggest that Aga1 and Aga2 play essential roles in the metabolism of dietary oligosaccharides and could be used for the design of galacto-oligosaccharide (GOS) prebiotics, known to selectively modulate the beneficial gut microbiota.T he human gut is colonized by a complex, diverse, and dynamic community of microbes that continuously interact with the host (30). The majority belongs to only four bacterial divisions, Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria, whereas other minor taxonomic divisions are quite diverse (19,43,62). Several ecological studies have shown that microbial symbionts have adapted to maximize metabolic access to a wide variety of dietary and host-derived carbohydrates (glycans), and competition for these nutrients is considered a major factor shaping the structure-function of the microbiota (33). Recently, a metagenomic analysis of gut microbial communities in humans proposed three predominant variants, or "enterotypes," dominated by Bacteroides, Prevotella, and Ruminococcus (3). A controlledfeeding study showed that enterotype partitioning associates with long-term diets (61). Furthermore, the ability to selectively use prebiotics carbohydrates, ranging from oligosaccharides to polysaccharides, provides a competitive advantage over other bacteria in this ecosystem (28). These studies highlight the importance of understanding precisely how nutrient metabolism serves to maintain a symbiotic relationship between gut bacteria and the host. The genomes of gut bacteria encode a wide array of carbohydrateactive enzymes (CAZymes) that d...

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Ruminococcin C, a new anti-Clostridium perfringens bacteriocin produced in the gut by the commensal bacterium Ruminococcus gnavus E1

Cited by 49 publications

References 33 publications

Small molecules from the human microbiota

Small molecules from the human microbiota

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

Functional Analysis of Family GH36 α-Galactosidases from Ruminococcus gnavus E1: Insights into the Metabolism of a Plant Oligosaccharide by a Human Gut Symbiont

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