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

Steve Chiumento (1) , Clarisse Roblin (2, 3) , Sylvie Kieffer-Jaquinod (4) , Sybille Tachon (2) , Chloé Leprêtre (1) , Christian Basset (1) , Dwi Aditiyarini (1) , Hamza Olleik (2) , Cendrine Nicoletti (2) , Olivier Bornet (5) , Olga Iranzo (2) , Marc Maresca (2) , Renaud Hardré (2) , Michel Fons (6) , Thierry Giardina (2) , Estelle Devillard (7) , Françoise Guerlesquin (8) , Yohann Couté (4) , Mohamed Atta (1) , Josette Perrier (2) , Mickael Lafond (2) , Victor Duarte (1)

1 BIOCAT - Biocatalyse
2 ISM2 - Institut des Sciences Moléculaires de Marseille
3 ADISSEO France SAS, Centre d’Expertise et de Recherche en Nutrition
4 EDyP - Etude de la dynamique des protéomes
5 IMM - Institut de Microbiologie de la Méditerranée
6 BIP - Bioénergétique et Ingénierie des Protéines
7 ADISSEO France SAS, Centre d’Expertise et de Recherche en Nutrition,
8 LISM - Laboratoire d'ingénierie des systèmes macromoléculaires

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.

Domaines: Biochimie, Biologie Moléculaire; Bactériologie

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 , 2019, 5 (9), pp.eaaw9969. ⟨10.1126/sciadv.aaw9969⟩. ⟨hal-02371747⟩