A type I 3’ UTR-derived sRNA is involved in heme metabolism and virulence in Staphylococcus aureus

Staphylococcus aureus is a pathogen responsible for a wide array of superficial to life-threatening infections. To efficiently adapt to environmental cues, a complex regulatory network is needed, involving among others regulatory RNAs (sRNAs). Here, we studied Srn_9342, an sRNA transcribed into two isoforms of different lengths and known to interact with RNAIII, leading to a modulation of δ-hemolysin production. We showed that the two isoforms are oppositely expressed in a growth phase-dependent manner. Then, we demonstrated using transcriptional fusions and various chromosomally recombinant strains that Srn_9342 is a type I 3’UTR-derived sRNA whose the expression of the long form (Srn_9342 _L ) is SigB-dependent. Using a Δsrn_9342 mutant, we monitored the transcript level of various RNA partners previously identified by MAPS and showed that the hemQ mRNA level, encoding a protein involved in heme biosynthesis and reported to participate in small colony variant (SCV) phenotype, increased in the mutant. In silico and in vitro biochemical investigations showed that a 5’ region of Srn_9342 binds hemQ leading to a repression of the HemQ protein level whereas the overexpression of Srn_9342 induced an SCV phenotype which was partially relieved by the addition of hemin. Finally, we report that the deletion of srn_9342 significantly increased the virulence of the pathogen in a Galleria mellonella model. Taking together, these data uncovered a novel type I 3’ UTR-derived sRNA regulating the heme biosynthesis pathway and implicated in virulence and SCV formation in S. aureus .