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

Archive ouverte

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

Edité par CCSD ; American Association for the Advancement of Science (AAAS) -

International audience. 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.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion