Ruminococcin C, a promising antibiotic produced by a human gut symbiont.
Steve ChiumentoClarisse RoblinSylvie Kieffer-JaquinodSybille TachonChloé LeprètreChristian BassetDwi AditiyariniHamza OlleikCendrine NicolettiOlivier BornetOlga IranzoMarc MarescaRenaud HardréMichel FonsThierry GiardinaEstelle DevillardFrançoise GuerlesquinYohann CoutMohamed AttaJosette PerrierMickael LafondVictor DuartePublished in: Science advances (2019)
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.
Keyphrases
- multidrug resistant
- public health
- endothelial cells
- staphylococcus aureus
- escherichia coli
- pluripotent stem cells
- drug resistant
- healthcare
- gram negative
- oxidative stress
- pseudomonas aeruginosa
- cystic fibrosis
- cell death
- risk assessment
- single molecule
- cell cycle arrest
- binding protein
- long non coding rna
- health promotion