PRJNA445980
The small RNA Teg41 regulates expression of the alpha Phenol Soluble Modulins (aPSMs) 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 (aPSM) peptides, plays a critical role in aPSM production. Overproduction of Teg41 leads to an increase in aPSM levels and a corresponding increase in hemolytic activity from S. aureus cells and cell-free culture supernatants. We demonstrate that the increase in aPSM production is post-transcriptional, as expression of the aPSM 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 aPSM 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 aPSM-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 aPSM peptides, demonstrating, for the first time, post-transcriptional regulation of the aPSM peptides by an sRNA in S. aureus.