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The unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties

Clarisse Roblin 1, 2 Steve Chiumento 3 Olivier Bornet 4, * Matthieu Nouailler 5 Christina S. Müller 6 Katy Jeannot 7, 8 Christian Basset 3 Sylvie Kieffer-Jaquinod 9 Yohann Couté 9 Stéphane Torelli 10 Laurent Le pape 10 Volker Schünemann 6 Hamza Olleik 1 Bruno de la Villeon 11 Philippe Sockeel 11 Eric Di Pasquale 12 Cendrine Nicoletti 1 Nicolas Vidal 13 Leonora Poljak 14 Olga Iranzo 1 Thierry Giardina 1 Michel Fons 15 Estelle Devillard 16 Patrice Polard 14 Marc Maresca 1 Josette Perrier 1 Mohamed Atta 3 Francoise Guerlesquin 5 Mickaël Lafond 1, * Victor Duarte 3, *
Abstract : 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.
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https://hal.archives-ouvertes.fr/hal-02920462
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Submitted on : Tuesday, December 8, 2020 - 4:01:15 PM
Last modification on : Wednesday, October 20, 2021 - 3:34:03 AM
Long-term archiving on: : Tuesday, March 9, 2021 - 7:46:16 PM

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Clarisse Roblin, Steve Chiumento, Olivier Bornet, Matthieu Nouailler, Christina S. Müller, et al.. The unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2020, 117 (32), pp.19168-19177. ⟨10.1073/pnas.2004045117⟩. ⟨hal-02920462⟩

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