The small RNA Teg41 regulates expression of the alpha Phenol Soluble Modulins (αPSMs) and is required for virulence in Staphylococcus aureus

Small RNAs (sRNAs) remain an understudied class of regulatory molecules in bacteria in general, and in Gram-positive bacteria in particular. In the major human pathogen Staphylococcus aureus hundreds of sRNAs have been identified, however, only a few have been characterized in detail. In this study we investigate the role of the sRNA Teg41 in S. aureus virulence. We demonstrate that Teg41, an sRNA divergently transcribed from the locus that encodes the cytolytic alpha phenol soluble modulin (αPSM) peptides, plays a critical role in αPSM production. Overproduction of Teg41 leads to an increase in αPSM levels and a corresponding increase in hemolytic activity from S. aureus cells and cell-free culture supernatants. We demonstrate that the increase in αPSM production is post-transcriptional, as expression of the αPSM transcript is unaltered upon Teg41 overproduction. To identify regions of Teg41 important for its function we performed an in silico RNA:RNA interaction analysis which predicted an interaction between the 3’ end of Teg41 and the αPSM transcript. Deleting a 24-nucleotide region from the S. aureus genome, corresponding to the 3’ end of Teg41, led to a 10-fold reduction in αPSM-dependent hemolytic activity and attenuation of virulence in a murine abscess model of infection. Our results strongly suggest that Teg41 is positively influencing translation of the αPSM peptides, demonstrating, for the first time, post-transcriptional regulation of the αPSM peptides by an sRNA in S. aureus.