6533b7ddfe1ef96bd12735b8
RESEARCH PRODUCT
The unusual structure of Ruminococcin C1 antimicrobial peptide confers clinical properties.
Christina S. MüllerPatrice PolardFrançoise GuerlesquinVolker SchünemannEric Di PasqualeBruno De La VilléonJosette PerrierMichel FonsMickael LafondOlivier BornetEstelle DevillardNicolas VidalYohann CoutéCendrine NicolettiLaurent Le PapeStéphane TorelliOlga IranzoKaty JeannotChristian BassetMarc MarescaMohamed AttaVictor DuarteClarisse RoblinHamza OlleikThierry GiardinaPhilippe SockeelSylvie Kieffer-jaquinodMatthieu NouaillerSteve ChiumentoLeonora Poljaksubject
0301 basic medicinemedicine.drug_class[CHIM.THER] Chemical Sciences/Medicinal ChemistryAntibioticsgut microbiomeContext (language use)Peptide[CHIM.THER]Chemical Sciences/Medicinal Chemistry010402 general chemistry01 natural sciencesMicrobiologyClostridia03 medical and health sciencesRuminococcus gnavusantibioticmedicineRiPPHumansIntestinal Mucosa[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitologychemistry.chemical_classificationRadical SAM enzymeClostridialesMultidisciplinarybiologyRiPPs Ruminococcin C sactipeptide gut microbiome antibiotic[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and GastroenterologyBacterial InfectionsBiological Sciencesbiology.organism_classificationAntimicrobialIntestinal epithelium[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology0104 chemical sciences3. Good healthsactipeptideAnti-Bacterial AgentsRuminococcus gnavusRiPPs030104 developmental biology[SDV.MP]Life Sciences [q-bio]/Microbiology and ParasitologychemistryRuminococcin CPeptidesBacteriadescription
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 introduced post-translationally 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-08-11 | Proceedings of the National Academy of Sciences of the United States of America |