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The Small RNA Teg41 Is a Pleiotropic Regulator of Virulence in Staphylococcus aureus [teg41 psm]

ABSTRACT: Staphylococcus aureus is Gram-positive commensal bacteria that can also cause human disease ranging from mild, self-resolving skin infections to life-threatening conditions like endocarditis, osteomyelitis, and septicemia. Previously we demonstrated a role for the S. aureus sRNA, Teg41 in regulating production of the alpha Phenol Soluble Modulin toxins (αPSMs). In this study, we further characterize the regulatory role of Teg41. RNAseq analysis shows Teg41 influences the abundance of not just the αPSM transcript, but a variety of other transcripts as well compared to wild type S. aureus. Proteomic analysis confirms that eliminating Teg41 from the cell influences both the cytoplasmic and secreted protein profile of S. aureus. Finally, we observe that the Teg41Δ3′ strain is more severely attenuated in two murine infection models than a ∆αPSM strain, indicating that Teg41 regulation reaches beyond the αPSMs. Overall, we show that Teg41 is a unique pleiotropic sRNA in S. aureus that influences several key cellular processes.

ORGANISM(S): Staphylococcus aureus

PROVIDER: GSE203563 | GEO | 2022/09/29

REPOSITORIES: GEO

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The Small RNA Teg41 Is a Pleiotropic Regulator of Virulence in Staphylococcus aureus [wt teg41]

Project description:Staphylococcus aureus is Gram-positive commensal bacteria that can also cause human disease ranging from mild, self-resolving skin infections to life-threatening conditions like endocarditis, osteomyelitis, and septicemia. Previously we demonstrated a role for the S. aureus sRNA, Teg41 in regulating production of the alpha Phenol Soluble Modulin toxins (αPSMs). In this study, we further characterize the regulatory role of Teg41. RNAseq analysis shows Teg41 influences the abundance of not just the αPSM transcript, but a variety of other transcripts as well compared to wild type S. aureus. Proteomic analysis confirms that eliminating Teg41 from the cell influences both the cytoplasmic and secreted protein profile of S. aureus. Finally, we observe that the Teg41Δ3′ strain is more severely attenuated in two murine infection models than a ∆αPSM strain, indicating that Teg41 regulation reaches beyond the αPSMs. Overall, we show that Teg41 is a unique pleiotropic sRNA in S. aureus that influences several key cellular processes.

2022-09-29 | GSE203564 | GEO

The small RNA Teg41 is a pleiotropic regulator of virulence in Staphylococcus aureus

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The small RNA Teg41 Regulates Expression of the alpha Phenol Soluble Modulins and is Required for Virulence in Staphylococcus aureus

Project description:Small RNAs (sRNAs) remain an understudied class of regulatory molecules in bacteria. Hundreds of sRNAs have been identified in the major human pathogen Staphylococcus aureus; 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. Together these results demonstrate, for the first time, post-transcriptional regulation of the αPSM peptides by an sRNA in S. aureus.

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Project description:In this study, we further characterize the regulation of the αPSM transcript by Teg41. We show that a single chromosomally integrated copy of Teg41 restores virulence, hemolysis, extracellular vesicle production, and αPSM production in a strain deleted for the 3’ end of Teg41 (Teg41Δ3′ strain). We show that substituting four Teg41 nucleotides in the predicted Teg41- αPSM interaction site abolishes increased hemolysis in a Teg41 overexpression strain. We go on to demonstrte that Teg41 expression influences both the stability and abundance of the αPSM transcript, and, interestingly, that the Teg41Δ3′ strain shows decreased stability in more than 50 transcripts and altered expression levels in over 900 transcripts when compared to wild type S. aureus. Finally, we observe that Teg41 plays a role in S. aureus stress response and that the Teg41Δ3′ strain is more severely attenuated in murine systemic infection than a ∆αPSM strain, indicating that Teg41 regulation reaches beyond the αPSMs. Overall, we show that Teg41 is a unique pleiotropic sRNA in S. aureus that influences several key cellular processes.

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