The unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties

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TitreThe unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties
Type de publicationJournal Article
Year of Publication2020
AuteursRoblin C, Chiumento S, Bornet O, Nouailler M, Mueller CS, Jeannot K, Basset C, Kieffer-Jaquinod S, Coute Y, Torelli S, Le Pape L, Schuenemann V, Olleik H, De La Villeon B, Sockeel P, Di Pasquale E, Nicoletti C, Vidal N, Poljak L, Iranzo O, Giardina T, Fons M, Devillard E, Polard P, Maresca M, Perrier J, Atta M, Guerlesquin F, Lafond M, Duarte V
JournalPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume117
Pagination19168-19177
Date PublishedAUG 11
Type of ArticleArticle
ISSN0027-8424
Mots-clésAntibiotic, gut microbiome, RiPPs, Ruminococcin C, sactipeptide
Résumé

The emergence of superbugs developing resistance to antibiotics and the resurgence of microbial infections have led scientists to start an antimicrobial arms race. In this context, we have previously identified an active RiPP, the Ruminococcin C1, naturally produced by Ruminococcus gnavus E1, a symbiont of the healthy human intestinal microbiota. This RiPP, subclassified as a sactipeptide, requires the host digestive system to become active against pathogenic Clostridia and multidrug-resistant strains. Here we report its unique compact structure on the basis of four intramolecular thioether bridges with reversed stereochemistry introduced posttranslationally by a specific radical-SAM sactisynthase. This structure confers to the Ruminococcin C1 important clinical properties including stability to digestive conditions and physicochemical treatments, a higher affinity for bacteria than simulated intestinal epithelium, a valuable activity at therapeutic doses on a range of clinical pathogens, mediated by energy resources disruption, and finally safety for human gut tissues.

DOI10.1073/pnas.2004045117