MassIVE

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ftp://massive-ftp.ucsd.edu/v07/MSV000094753/primaryOK200Jeffrey L. Bosehttps://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=389c4525d1054c6ea420a5e98cbb78f3jbose@kumc.eduMassIVE21UNIMOD:4 - "Iodoacetamide derivative."UNIMOD:35 - "Oxidation or Hydroxylation."ProteomicsOrbitrap AscendStaphylococcus Aureus Subsp. Aureus Usa300 (ncbitaxon:367830)University of Kansas Medical CenterStaphylococcus aureus is the most common cause of skin and soft tissue infections (SSTIs) with Methicillin-Resistant S. aureus (MRSA) strains being a major contributor in both community and hospital settings. S. aureus relies on metabolic diversity and a large repertoire of virulence factors to cause disease. This includes α-hemolysin (Hla), an integral player in tissue damage found in various models, including SSTIs. Previously, we identified a role for the Spx adapter protein, YjbH, in the regulation of several virulence factors and as an inhibitor of pathogenesis in a sepsis model. In this study, we found that YjbH is critical for tissue damage during SSTI, and its absence leads to decreased proinflammatory chemokines and cytokines in the skin. We identified no contribution of YjbI, encoded on the same transcript as YjbH. Using a combination of reporters and quantitative hemolysis assays, we demonstrated that YjbH impacts Hla expression and activity both in vitro and in vivo. Additionally, expression of Hla from a non-native promoter reversed the tissue damage phenotype of the ΔyjbIH mutant. Lastly, we identified reduced Agr activity as the likely cause for reduced Hla production in the ΔyjbH mutant. This work continues to define the importance of YjbH in the pathogenesis of S. aureus infection as well as identify a new pathway important for Hla production.YjbH contributes to Staphylococcus aureus skin pathology and immune response through Agr-mediated α-toxin regulation.McReynolds Aubrey K G AKG, Pagella Emma A EA, Ridder Miranda J MJ, Rippee Olivia O, Clark Zachary Z, Rekowski Michaella J MJ, Pritchard Michele T MT, Bose Jeffrey L JLPXD052261falseYjbH contributes to S. aureus skin pathology and immune response through Agr-mediated alpha-toxin regulationStaphylococcus aureus is a global health threat that can cause a multitude of diseases in many different areas of the body and is the leading cause of skin infections. This bacterium can produce a variety of proteins that contribute to virulence and disease progression. These virulence factors include alpha-hemolysin (Hla), which can kill many different cell types in the human body. In this study, we identified a new protein that contributes to Hla production, YjbH. It does so by controlling the activity of the Accessory Gene Regulator (Agr), a major player in the modulation of proteins produced in the bacterium. We demonstrate that without YjbH, S. aureus cultures produce less Hla, and this is corroborated during infection. Accordingly, when YjbH is present, tissue damage is greater during infection than when it is absent. Overall, our study sheds light on the complex regulation involved in virulence factor production by S. aureus and its ability to cause a wide range of diseases. Tue May 14 08:03:00 BST 2024MSV00009475339229975