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

Autor:	Chiumento S; Univ. Grenoble Alpes, CEA, CNRS, CBM-UMR5249, 38000 Grenoble, France., Roblin C; Aix-Marseille Univ., CNRS, Centrale Marseille, iSm2, Marseille, France.; ADISSEO France SAS, Centre d'Expertise et de Recherche en Nutrition, Commentry, France., Kieffer-Jaquinod S; Univ. Grenoble Alpes, CEA, INSERM, BGE U1038, 38000 Grenoble, France., Tachon S; Aix-Marseille Univ., CNRS, Centrale Marseille, iSm2, Marseille, France., Leprètre C; Univ. Grenoble Alpes, CEA, CNRS, CBM-UMR5249, 38000 Grenoble, France., Basset C; Univ. Grenoble Alpes, CEA, CNRS, CBM-UMR5249, 38000 Grenoble, France., Aditiyarini D; Univ. Grenoble Alpes, CEA, CNRS, CBM-UMR5249, 38000 Grenoble, France., Olleik H; Aix-Marseille Univ., CNRS, Centrale Marseille, iSm2, Marseille, France., Nicoletti C; Aix-Marseille Univ., CNRS, Centrale Marseille, iSm2, Marseille, France., Bornet O; LISM, IMM, Aix-Marseille Univ., CNRS, Marseille, France., Iranzo O; Aix-Marseille Univ., CNRS, Centrale Marseille, iSm2, Marseille, France., Maresca M; Aix-Marseille Univ., CNRS, Centrale Marseille, iSm2, Marseille, France., Hardré R; Aix-Marseille Univ., CNRS, Centrale Marseille, iSm2, Marseille, France., Fons M; Unité de Bioénergétique et Ingénierie des Protéines UMR7281, Institut de Microbiologie de la Méditerranée, Aix-Marseille Univ., CNRS, Marseille, France., Giardina T; Aix-Marseille Univ., CNRS, Centrale Marseille, iSm2, Marseille, France., Devillard E; ADISSEO France SAS, Centre d'Expertise et de Recherche en Nutrition, Commentry, France., Guerlesquin F; LISM, IMM, Aix-Marseille Univ., CNRS, Marseille, France., Couté Y; Univ. Grenoble Alpes, CEA, INSERM, BGE U1038, 38000 Grenoble, France., Atta M; Univ. Grenoble Alpes, CEA, CNRS, CBM-UMR5249, 38000 Grenoble, France., Perrier J; Aix-Marseille Univ., CNRS, Centrale Marseille, iSm2, Marseille, France., Lafond M; Aix-Marseille Univ., CNRS, Centrale Marseille, iSm2, Marseille, France., Duarte V; Univ. Grenoble Alpes, CEA, CNRS, CBM-UMR5249, 38000 Grenoble, France.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2019 Sep 25; Vol. 5 (9), pp. eaaw9969. Date of Electronic Publication: 2019 Sep 25 (Print Publication: 2019).
DOI:	10.1126/sciadv.aaw9969
Abstrakt:	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. (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu