The Small RNA Teg41 Regulates Expression of the Alpha Phenol-Soluble Modulins and Is Required for Virulence in <named-content content-type="genus-species">Staphylococcus aureus</named-content>
ABSTRACT 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 th...
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American Society for Microbiology
2019
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oai:doaj.org-article:c89ede5aaffe46dea62094b8b9b4a5292021-11-15T15:55:14ZThe Small RNA Teg41 Regulates Expression of the Alpha Phenol-Soluble Modulins and Is Required for Virulence in <named-content content-type="genus-species">Staphylococcus aureus</named-content>10.1128/mBio.02484-182150-7511https://doaj.org/article/c89ede5aaffe46dea62094b8b9b4a5292019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02484-18https://doaj.org/toc/2150-7511ABSTRACT 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. 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. Restoration of hemolytic activity in the Teg41Δ3′ strain was possible by expressing full-length Teg41 in trans. Restoration of hemolytic activity was also possible by expressing the 3′ end of Teg41, suggesting that this region of Teg41 is necessary and sufficient for αPSM-dependent hemolysis. Our results show that Teg41 is positively influencing αPSM production, demonstrating for the first time regulation of the αPSM peptides by an sRNA in S. aureus. IMPORTANCE The alpha phenol-soluble modulins (αPSMs) are among the most potent toxins produced by Staphylococcus aureus. Their biological role during infection has been studied in detail; however, the way they are produced by the bacterial cell is not well understood. In this work, we identify a small RNA molecule called Teg41 that plays an important role in αPSM production by S. aureus. Teg41 positively influences αPSM production. The importance of Teg41 is highlighted by the fact that a strain containing a deletion in the 3′ end of Teg41 produces significantly less αPSMs and is attenuated for virulence in a mouse abscess model of infection. As the search for new therapeutic strategies to combat S. aureus infection proceeds, Teg41 may represent a novel target.Rachel L. ZapfRichard E. WiemelsRebecca A. KeoghDonald L. HolzschuKayla M. HowellEmily TrzeciakAndrew R. CailletKellie A. KingSamantha A. SelhorstMichael J. NaldrettJeffrey L. BoseRonan K. CarrollAmerican Society for MicrobiologyarticlePSMStaphylococcus aureusTeg41phenol-soluble modulinregulatory RNAsRNAMicrobiologyQR1-502ENmBio, Vol 10, Iss 1 (2019) |
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| collection |
DOAJ |
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EN |
| topic |
PSM Staphylococcus aureus Teg41 phenol-soluble modulin regulatory RNA sRNA Microbiology QR1-502 |
| spellingShingle |
PSM Staphylococcus aureus Teg41 phenol-soluble modulin regulatory RNA sRNA Microbiology QR1-502 Rachel L. Zapf Richard E. Wiemels Rebecca A. Keogh Donald L. Holzschu Kayla M. Howell Emily Trzeciak Andrew R. Caillet Kellie A. King Samantha A. Selhorst Michael J. Naldrett Jeffrey L. Bose Ronan K. Carroll The Small RNA Teg41 Regulates Expression of the Alpha Phenol-Soluble Modulins and Is Required for Virulence in <named-content content-type="genus-species">Staphylococcus aureus</named-content> |
| description |
ABSTRACT 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. 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. Restoration of hemolytic activity in the Teg41Δ3′ strain was possible by expressing full-length Teg41 in trans. Restoration of hemolytic activity was also possible by expressing the 3′ end of Teg41, suggesting that this region of Teg41 is necessary and sufficient for αPSM-dependent hemolysis. Our results show that Teg41 is positively influencing αPSM production, demonstrating for the first time regulation of the αPSM peptides by an sRNA in S. aureus. IMPORTANCE The alpha phenol-soluble modulins (αPSMs) are among the most potent toxins produced by Staphylococcus aureus. Their biological role during infection has been studied in detail; however, the way they are produced by the bacterial cell is not well understood. In this work, we identify a small RNA molecule called Teg41 that plays an important role in αPSM production by S. aureus. Teg41 positively influences αPSM production. The importance of Teg41 is highlighted by the fact that a strain containing a deletion in the 3′ end of Teg41 produces significantly less αPSMs and is attenuated for virulence in a mouse abscess model of infection. As the search for new therapeutic strategies to combat S. aureus infection proceeds, Teg41 may represent a novel target. |
| format |
article |
| author |
Rachel L. Zapf Richard E. Wiemels Rebecca A. Keogh Donald L. Holzschu Kayla M. Howell Emily Trzeciak Andrew R. Caillet Kellie A. King Samantha A. Selhorst Michael J. Naldrett Jeffrey L. Bose Ronan K. Carroll |
| author_facet |
Rachel L. Zapf Richard E. Wiemels Rebecca A. Keogh Donald L. Holzschu Kayla M. Howell Emily Trzeciak Andrew R. Caillet Kellie A. King Samantha A. Selhorst Michael J. Naldrett Jeffrey L. Bose Ronan K. Carroll |
| author_sort |
Rachel L. Zapf |
| title |
The Small RNA Teg41 Regulates Expression of the Alpha Phenol-Soluble Modulins and Is Required for Virulence in <named-content content-type="genus-species">Staphylococcus aureus</named-content> |
| title_short |
The Small RNA Teg41 Regulates Expression of the Alpha Phenol-Soluble Modulins and Is Required for Virulence in <named-content content-type="genus-species">Staphylococcus aureus</named-content> |
| title_full |
The Small RNA Teg41 Regulates Expression of the Alpha Phenol-Soluble Modulins and Is Required for Virulence in <named-content content-type="genus-species">Staphylococcus aureus</named-content> |
| title_fullStr |
The Small RNA Teg41 Regulates Expression of the Alpha Phenol-Soluble Modulins and Is Required for Virulence in <named-content content-type="genus-species">Staphylococcus aureus</named-content> |
| title_full_unstemmed |
The Small RNA Teg41 Regulates Expression of the Alpha Phenol-Soluble Modulins and Is Required for Virulence in <named-content content-type="genus-species">Staphylococcus aureus</named-content> |
| title_sort |
small rna teg41 regulates expression of the alpha phenol-soluble modulins and is required for virulence in <named-content content-type="genus-species">staphylococcus aureus</named-content> |
| publisher |
American Society for Microbiology |
| publishDate |
2019 |
| url |
https://doaj.org/article/c89ede5aaffe46dea62094b8b9b4a529 |
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