Barrault, M.; Leclair, E.; Bouloc, P.

Staphylococcus aureus is a major contributor to bacterial-associated mortality, owing to its exceptional adaptability across diverse environments. Iron, vital for most organisms, poses toxicity risks in excess. To manage iron, S. aureus, like many pathogens, employs intricate systems. We have recently identified IsrR as a key regulatory RNA induced during iron starvation. Its role is to curtail the synthesis of non-essential iron-containing proteins under iron-depleted conditions. In this study, we unveil IsrR\'s regulatory action on MiaB, an enzyme responsible for methylthio group addition to specific sites on transfer RNAs (tRNAs). We use predictive tools and reporter fusion assays to demonstrate IsrR\'s binding to the Shine-Dalgarno sequence of miaB RNA, thereby impeding its translation. The effectiveness of IsrR hinges on the integrity of a specific C-rich region. As MiaB is non-essential and contains two [4Fe-4S] clusters, IsrR induction spares iron by downregulating miaB. This likely enhances S. aureus fitness and aids in navigating the host\'s nutritional immune defenses.