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Staphylococcus aureus SigS Induces Expression of a Regulatory Protein Pair That Modulates Its mRNA Stability.
Al Ali, Amer; Alsulami, Jamilah; Aubee, Joseph I; Idowu, Ayotimofe; Tomlinson, Brooke R; Felton, Emily A; Jackson, Jessica K; Kennedy, Sarah J; Torres, Nathanial J; Shaw, Lindsey N; Thompson, Karl M.
Afiliação
  • Al Ali A; Department of Microbiology, College of Medicine, Howard University, Washington, DC, USA.
  • Alsulami J; Department of Microbiology, College of Medicine, Howard University, Washington, DC, USA.
  • Aubee JI; Department of Microbiology, College of Medicine, Howard University, Washington, DC, USA.
  • Idowu A; Department of Biology, College of Arts and Sciences, Howard University, Washington, DC, USA.
  • Tomlinson BR; Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, Florida, USA.
  • Felton EA; Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, Florida, USA.
  • Jackson JK; Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, Florida, USA.
  • Kennedy SJ; Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, Florida, USA.
  • Torres NJ; Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, Florida, USA.
  • Shaw LN; Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, Florida, USA.
  • Thompson KM; Department of Microbiology, College of Medicine, Howard University, Washington, DC, USA.
J Bacteriol ; 205(6): e0039222, 2023 06 27.
Article em En | MEDLINE | ID: mdl-37255480
ABSTRACT
SigS is the sole extracytoplasmic function sigma factor in Staphylococcus aureus and is necessary for virulence, immune evasion, and adaptation to toxic chemicals and environmental stressors. Despite the contribution of SigS to a myriad of critical phenotypes, the downstream effectors of SigS-dependent pathogenesis, immune evasion, and stress adaptation remain elusive. To address this knowledge gap, we analyzed the S. aureus transcriptome following transient overexpression of SigS. We identified a bicistronic transcript, upregulated 1,000-fold, containing two midsized genes, each containing single domains of unknown function (DUFs). We renamed these genes SigS-regulated orfA (sroA) and SigS-regulated orfB (sroB). We demonstrated that SigS regulation of the sroAB operon is direct by using in vitro transcription analysis. Using Northern blot analysis, we also demonstrated that SroA and SroB have opposing autoregulatory functions on the transcriptional architecture of the sigS locus, with SroA stimulating SigS mRNA levels and SroB stimulating s750 (SigS antisense) levels. We hypothesized that these opposing regulatory effects were due to a direct interaction. We subsequently demonstrated a direct interaction between SroA and SroB using an in vivo surrogate genetics approach via bacterial adenylate cyclase-based two-hybrid (BACTH) analysis. We demonstrated that the SroA effect on SigS is at the posttranscriptional level of mRNA stability, highlighting a mechanism likely used by S. aureus to tightly control SigS levels. Finally, we demonstrate that the sroAB locus promotes virulence in a murine pneumonia model of infection. IMPORTANCE SigS is necessary for S. aureus virulence, immune evasion, and adaptation to chemical and environmental stressors. These processes are critically important for the ability of S. aureus to cause disease. However, the SigS-dependent transcriptome has not been identified, hindering our ability to identify downstream effectors of SigS that contribute to these pathogenic and adaptive phenotypes. Here, we identify a regulatory protein pair that is a major direct target of SigS, known as SroA and SroB. SroA also acts to stimulate SigS expression at the posttranscriptional level of RNA turnover, providing insight into intrinsically low levels of SigS. The discovery of SroA and SroB increases our understanding of SigS and the S. aureus pathogenesis process.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções Estafilocócicas / Staphylococcus aureus Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Infecções Estafilocócicas / Staphylococcus aureus Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article