Germain Maëliss, Robin Hugo, Le Huyen Kim Boi, Massier Sébastien, Nalpas Nicolas, Hardouin Julie, Bouloc Philippe, Rouillon Astrid, Chabelskaya Svetlana
Inserm, University of Rennes, BRM (Bacterial RNAs and Medicine) UMR_S1230, Rennes 35043, France.
University of Rouen Normandie, INSERM US 51, CNRS UAR 2026, HeRacLeS-PISSARO, Normandie University, Rouen 76000, France.
Nucleic Acids Res. 2025 Jul 8;53(13). doi: 10.1093/nar/gkaf616.
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 aureus has 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 of S. aureus under 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 base pairing 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.
金黄色葡萄球菌是一种机会致病菌，可导致人类多种疾病。在感染过程中，这种细菌会面临各种针对其细胞壁的压力，如氧化或酸性环境以及各种作用于细胞壁的抗菌药物。金黄色葡萄球菌具有有效的调节系统来应对环境压力，从而能够表达其生存所需的因子。细菌小RNA（sRNA）在这一适应过程中起着关键作用。在本研究中，我们发现金黄色葡萄球菌的sRNA RsaOI在酸性应激条件下会积累。这种反应是通过与细胞壁损伤反应相关的双组分系统VraSR介导的。作为VraSR调控子的一个组成部分，RsaOI有助于金黄色葡萄球菌在酸性应激下存活，并影响其对糖肽类抗生素的敏感性。我们的研究结果表明，RsaOI靶向编码塔格糖途径成分的lacABCDFEG操纵子，这是金黄色葡萄球菌中负责半乳糖代谢的独特机制。通过在lacD的核糖体结合位点附近进行反义碱基配对，RsaOI抑制了该基因（编码塔格糖-6-磷酸醛缩酶）的表达。这种调控破坏了塔格糖途径，损害了金黄色葡萄球菌对半乳糖的利用。这些发现突出了RsaOI在细胞壁应激反应与特定代谢途径之间的介导作用。
