| Autor: |
Briaud P; Department of Biological Sciences, Ohio Universitygrid.20627.31, Athens, Ohio, USA., Zapf RL; Department of Biological Sciences, Ohio Universitygrid.20627.31, Athens, Ohio, USA., Mayher AD; Department of Biological Sciences, Ohio Universitygrid.20627.31, Athens, Ohio, USA.; Molecular and Cellular Biology Program, Ohio Universitygrid.20627.31, Athens, Ohio, USA., McReynolds AKG; Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA., Frey A; Department of Cell Biology, Microbiology, and Molecular Biology, University of South Floridagrid.170693.a, Tampa, Florida, USA., Sudnick EG; Department of Biological Sciences, Ohio Universitygrid.20627.31, Athens, Ohio, USA., Wiemels RE; Department of Biological Sciences, Ohio Universitygrid.20627.31, Athens, Ohio, USA., Keogh RA; Department of Biological Sciences, Ohio Universitygrid.20627.31, Athens, Ohio, USA., Shaw LN; Department of Cell Biology, Microbiology, and Molecular Biology, University of South Floridagrid.170693.a, Tampa, Florida, USA., Bose JL; Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA., Carroll RK; Department of Biological Sciences, Ohio Universitygrid.20627.31, Athens, Ohio, USA.; Molecular and Cellular Biology Program, Ohio Universitygrid.20627.31, Athens, Ohio, USA.; Infectious and Tropical Disease Institute, Ohio Universitygrid.20627.31, Athens, Ohio, USA. |
| Abstrakt: |
Previously, our group demonstrated a role for the small RNA (sRNA) Teg41 in regulating production of the alpha phenol-soluble modulin toxins (αPSMs) in Staphylococcus aureus. Overexpressing Teg41 increased αPSM production while deleting the 3' end of Teg41 (Teg41Δ3' strain) resulted in a decrease in αPSM production, reduced hemolytic activity of S. aureus culture supernatants, and attenuated virulence in a murine abscess model of infection. In this study, we further explore the attenuation of virulence in the Teg41Δ3' strain. Using both localized and systemic models of infection, we demonstrate that the Teg41Δ3' strain is more severely attenuated than an ΔαPSM mutant, strongly suggesting that Teg41 influences more than the αPSMs. Proteomic and transcriptomic analysis of the wild-type and Teg41Δ3' strains reveals widespread alterations in transcript abundance and protein production in the absence of Teg41, confirming that Teg41 has pleiotropic effects in the cell. We go on to investigate the molecular mechanism underlying Teg41-mediated gene regulation. Surprisingly, results demonstrate that certain Teg41 target genes, including the αPSMs and βPSMs, are transcriptionally altered in the Teg41Δ3' strain, while other targets, specifically spa (encoding surface protein A), are regulated at the level of transcript stability. Collectively, these data demonstrate that Teg41 is a pleiotropic RNA regulator in S. aureus that influences expression of a variety of genes using multiple different mechanisms. |
