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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.

Author information

1
Univ. Grenoble Alpes, CEA, CNRS, CBM-UMR5249, 38000 Grenoble, France.
2
Aix-Marseille Univ., CNRS, Centrale Marseille, iSm2, Marseille, France.
3
ADISSEO France SAS, Centre d'Expertise et de Recherche en Nutrition, Commentry, France.
4
Univ. Grenoble Alpes, CEA, INSERM, BGE U1038, 38000 Grenoble, France.
5
LISM, IMM, Aix-Marseille Univ., CNRS, Marseille, France.
6
Unité de Bioénergétique et Ingénierie des Protéines UMR7281, Institut de Microbiologie de la Méditerranée, Aix-Marseille Univ., CNRS, Marseille, France.

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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