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Ruminococcin C, a promising antibiotic produced by a human gut symbiont

Abstract : A major public health challenge today is the resurgence of microbial infections caused by multidrug-resistant strains. Consequently, novel antimicrobial molecules are actively sought for development. In this context, the human gut microbiome is an under-explored potential trove of valuable natural molecules, such as the ribosomally-synthesized and post-translationally modified peptides (RiPPs). The biological activity of the sactipeptide subclass of RiPPs remains under-characterized. Here, we characterize an antimicrobial sactipeptide, Ruminococcin C1, purified from the caecal contents of rats mono-associated with Ruminococcus gnavus E1, a human symbiont. Its heterologous expression and post-translational maturation involving a specific sactisynthase establish a thioether network, which creates a double-hairpin folding. This original structure confers activity against pathogenic Clostridia and multidrug-resistant strains but no toxicity towards eukaryotic cells. Therefore, the Ruminococcin C1 should be considered as a valuable candidate for drug development and its producer strain R. gnavus E1 as a relevant probiotic for gut health enhancement.
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https://hal.archives-ouvertes.fr/hal-02371747
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Submitted on : Wednesday, November 20, 2019 - 9:35:29 AM
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Steve Chiumento, Clarisse Roblin, Sylvie Kieffer-Jaquinod, Sybille Tachon, Chloé Leprêtre, et al.. Ruminococcin C, a promising antibiotic produced by a human gut symbiont. Science Advances , American Association for the Advancement of Science (AAAS), 2019, 5 (9), pp.eaaw9969. ⟨10.1126/sciadv.aaw9969⟩. ⟨hal-02371747⟩

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