sRNA-mediated crosstalk between cell wall stress and galactose metabolism inStaphylococcus aureus

Abstract

Staphylococcus aureusis an opportunistic pathogen responsible for a wide range of infections in the human host. During infections, this bacterium is exposed to various stresses that target its cell wall, such as antibiotics, as well as environmental factors like acidification.S. aureuspossesses effective regulatory systems to respond to the environmental stresses by expressing the factors necessary for its survival. Small RNAs (sRNAs) play a crucial role in bacterial adaptation processes by modulating bacterial physiology to respond to environmental stress. In this study, we describe RsaOI, a sRNA ofS. aureusaccumulated under acid stress conditions. We have shown that two-component system VraSR, involved in cell wall damage response, is also activated under acidic conditions and controlsrsaOIexpression. As a component of the VraSR-controlled regulon, RsaOI influences the survival ofS. aureusunder acid stress and affects its susceptibility to glycopeptide antibiotics. Our findings reveal that RsaOI targetslacABCDFEGoperon, constituting the unique mechanism responsible for galactose metabolism inS. aureusnamed tagatose pathway. By antisense base pairing near the ribosome-binding site oflacD, RsaOI inhibits the expression of this gene, encoding tagatose-6-phosphate aldolase. This regulation disrupts the tagatose pathway, impairing galactose utilization inS. aureus. Furthermore, we demonstrated that disruption of thelacoperon repression leads to significant alterations in the cell morphology and cell envelope structure. These findings highlight the role of RsaOI in the mediation between cell wall stress responses and specific metabolic pathway.