Rennes University, lab. BRM (Bacterial RNAs in Medicine) sRNA-mediated crosstalk between cell wall stress and galactose metabolism in Staphylococcus aureus.
Nucleic Acids Res. 2025 Jul 8;53(13):gkaf616. doi: 10.1093/nar/gkaf616. PMID: 40671522; PMCID: PMC12266140. Germain M, Robin H, Le Huyen KB, Massier S, Nalpas N, Hardouin J, Bouloc P, Rouillon A, Chabelskaya S
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Maëliss Germain, 31, holds a PhD in Microbiology and Molecular Biology. After completing a Bachelor’s degree in Microbiology and a Master’s degree focused on microbial molecular mechanisms at the University of Caen, she developed a strong interest in the mechanistic choreography that orchestrates the regulation of pathogenic bacteria. Driven by this curiosity for bacterial regulatory networks, she pursued her PhD at the University of Rennes within the BRM laboratory (Bacterial RNAs in Medicine), under the supervision of Dr. Svetlana Chabelskaia. Her research focused on the characterization of a poorly described regulatory RNA, RsaOI, in the pathogenic and multidrug-resistant bacterium Staphylococcus aureus. She revealed its role in cell wall stress management, particularly in response to acid stress and antibiotics targeting the cell wall, such as glycopeptides, as well as its connection to galactose metabolism. This work resulted in a publication in Nucleic Acids Research. Maëliss will soon join Patrick Viollier’s laboratory in Geneva, where she will pursue a postdoctoral fellowship dedicated to the in-depth exploration of the transcriptional machinery in obligate intracellular bacteria.
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Résumé de l'article
Staphylococcus aureus is an opportunistic pathogen responsible for a wide range of diseases in humans. During infections, this bacterium is exposed to various stresses that target its cell wall, such as oxidative or acid environments as well as various cell wall- acting antimicrobials.Staphylococcus aureushas effective regulatory systems for responding to environmental stresses, enabling the expression of factors necessary for its survival. Bacterial small RNAs (sRNAs) play a crucial role in this adaptation process. In this study, we show that RsaOI, an S. aureus sRNA, accumulates under acid stress conditions. This response is mediated via the two-component system VraSR, which is associated with the cell wall damage response. As a component of the VraSR regulon, RsaOI contributes to the survival ofS. aureusunder acid stress and affects its susceptibility to glycopeptide antibiotics. Our findings reveal that RsaOI targets the lacABCDFEG operon, which encodes components of tagatose pathway, a unique mechanism responsible for galactose metabolism in S. aureus. By antisense basepairing near the ribosome binding site of lacD, RsaOI inhibits the expression of this gene, encoding tagatose-6-phosphate aldolase. This regulation disrupts the tagatose pathway, impairing galactose utilization in S. aureus. These findings highlight the role of RsaOI in the mediation between cell wall stress responses and a specific metabolic pathway.
