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Sci Adv. 2019 Sep 25;5(9):eaaw9969. doi: 10.1126/sciadv.aaw9969. eCollection 2019 Sep.

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

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Univ. Grenoble Alpes, CEA, CNRS, CBM-UMR5249, 38000 Grenoble, France.
Aix-Marseille Univ., CNRS, Centrale Marseille, iSm2, Marseille, France.
ADISSEO France SAS, Centre d'Expertise et de Recherche en Nutrition, Commentry, France.
Univ. Grenoble Alpes, CEA, INSERM, BGE U1038, 38000 Grenoble, France.
LISM, IMM, Aix-Marseille Univ., CNRS, Marseille, France.
Unité de Bioénergétique et Ingénierie des Protéines UMR7281, Institut de Microbiologie de la Méditerranée, Aix-Marseille Univ., CNRS, Marseille, France.


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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