The Small Protein ScrA Influences Staphylococcus aureus Virulence-Related Processes via the SaeRS System
ABSTRACT Staphylococcus aureus is a Gram-positive commensal and opportunistic pathogen able to cause diseases ranging from mild skin infections to life-threatening endocarditis and toxic shock syndrome. The ability to cause such an array of diseases is due to the complex S. aureus regulatory network...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2023-06-01
|
| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.05255-22 |
| _version_ | 1827925093323374592 |
|---|---|
| author | Marcus A. Wittekind Paul Briaud Jayanna L. Smith Julia R. Tennant Ronan K. Carroll |
| author_facet | Marcus A. Wittekind Paul Briaud Jayanna L. Smith Julia R. Tennant Ronan K. Carroll |
| author_sort | Marcus A. Wittekind |
| collection | DOAJ |
| description | ABSTRACT Staphylococcus aureus is a Gram-positive commensal and opportunistic pathogen able to cause diseases ranging from mild skin infections to life-threatening endocarditis and toxic shock syndrome. The ability to cause such an array of diseases is due to the complex S. aureus regulatory network controlling an assortment of virulence factors, including adhesins, hemolysins, proteases, and lipases. This regulatory network is controlled by both protein and RNA elements. We previously identified a novel regulatory protein called ScrA, which, when overexpressed, leads to the increased activity and expression of the SaeRS regulon. In this study, we further explore the role of ScrA and examine the consequences to the bacterial cell of scrA gene disruption. These results demonstrate that scrA is required for several virulence-related processes, and in many cases, the phenotypes of the scrA mutant are inverse to those observed in cells overexpressing ScrA. Interestingly, while the majority of ScrA-mediated phenotypes appear to rely on the SaeRS system, our results also indicate that ScrA may also act independently of SaeRS when regulating hemolytic activity. Finally, using a murine model of infection, we demonstrate that scrA is required for virulence, potentially in an organ-specific manner. IMPORTANCE Staphylococcus aureus is the cause of several potentially life-threatening infections. An assortment of toxins and virulence factors allows such a wide range of infections. However, an assortment of toxins or virulence factors requires complex regulation to control expression under all of the different conditions encountered by the bacterium. Understanding the intricate web of regulatory systems allows the development of novel approaches to combat S. aureus infections. Here, we have shown that the small protein ScrA, which was previously identified by our laboratory, influences several virulence-related functions through the SaeRS global regulatory system. These findings add ScrA to the growing list of virulence regulators in S. aureus. |
| first_indexed | 2024-03-13T05:21:27Z |
| format | Article |
| id | doaj.art-85c91101c51145bd93230f34bac5b127 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-13T05:21:27Z |
| publishDate | 2023-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-85c91101c51145bd93230f34bac5b1272023-06-15T13:18:32ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-06-0111310.1128/spectrum.05255-22The Small Protein ScrA Influences Staphylococcus aureus Virulence-Related Processes via the SaeRS SystemMarcus A. Wittekind0Paul Briaud1Jayanna L. Smith2Julia R. Tennant3Ronan K. Carroll4Department of Biological Sciences, Ohio University, Athens, Ohio, USADepartment of Biological Sciences, Ohio University, Athens, Ohio, USADepartment of Biological Sciences, Ohio University, Athens, Ohio, USADepartment of Biological Sciences, Ohio University, Athens, Ohio, USADepartment of Biological Sciences, Ohio University, Athens, Ohio, USAABSTRACT Staphylococcus aureus is a Gram-positive commensal and opportunistic pathogen able to cause diseases ranging from mild skin infections to life-threatening endocarditis and toxic shock syndrome. The ability to cause such an array of diseases is due to the complex S. aureus regulatory network controlling an assortment of virulence factors, including adhesins, hemolysins, proteases, and lipases. This regulatory network is controlled by both protein and RNA elements. We previously identified a novel regulatory protein called ScrA, which, when overexpressed, leads to the increased activity and expression of the SaeRS regulon. In this study, we further explore the role of ScrA and examine the consequences to the bacterial cell of scrA gene disruption. These results demonstrate that scrA is required for several virulence-related processes, and in many cases, the phenotypes of the scrA mutant are inverse to those observed in cells overexpressing ScrA. Interestingly, while the majority of ScrA-mediated phenotypes appear to rely on the SaeRS system, our results also indicate that ScrA may also act independently of SaeRS when regulating hemolytic activity. Finally, using a murine model of infection, we demonstrate that scrA is required for virulence, potentially in an organ-specific manner. IMPORTANCE Staphylococcus aureus is the cause of several potentially life-threatening infections. An assortment of toxins and virulence factors allows such a wide range of infections. However, an assortment of toxins or virulence factors requires complex regulation to control expression under all of the different conditions encountered by the bacterium. Understanding the intricate web of regulatory systems allows the development of novel approaches to combat S. aureus infections. Here, we have shown that the small protein ScrA, which was previously identified by our laboratory, influences several virulence-related functions through the SaeRS global regulatory system. These findings add ScrA to the growing list of virulence regulators in S. aureus.https://journals.asm.org/doi/10.1128/spectrum.05255-22SaeRSScrAStaphylococcus aureusclumpinggene regulationhemolysis |
| spellingShingle | Marcus A. Wittekind Paul Briaud Jayanna L. Smith Julia R. Tennant Ronan K. Carroll The Small Protein ScrA Influences Staphylococcus aureus Virulence-Related Processes via the SaeRS System Microbiology Spectrum SaeRS ScrA Staphylococcus aureus clumping gene regulation hemolysis |
| title | The Small Protein ScrA Influences Staphylococcus aureus Virulence-Related Processes via the SaeRS System |
| title_full | The Small Protein ScrA Influences Staphylococcus aureus Virulence-Related Processes via the SaeRS System |
| title_fullStr | The Small Protein ScrA Influences Staphylococcus aureus Virulence-Related Processes via the SaeRS System |
| title_full_unstemmed | The Small Protein ScrA Influences Staphylococcus aureus Virulence-Related Processes via the SaeRS System |
| title_short | The Small Protein ScrA Influences Staphylococcus aureus Virulence-Related Processes via the SaeRS System |
| title_sort | small protein scra influences staphylococcus aureus virulence related processes via the saers system |
| topic | SaeRS ScrA Staphylococcus aureus clumping gene regulation hemolysis |
| url | https://journals.asm.org/doi/10.1128/spectrum.05255-22 |
| work_keys_str_mv | AT marcusawittekind thesmallproteinscrainfluencesstaphylococcusaureusvirulencerelatedprocessesviathesaerssystem AT paulbriaud thesmallproteinscrainfluencesstaphylococcusaureusvirulencerelatedprocessesviathesaerssystem AT jayannalsmith thesmallproteinscrainfluencesstaphylococcusaureusvirulencerelatedprocessesviathesaerssystem AT juliartennant thesmallproteinscrainfluencesstaphylococcusaureusvirulencerelatedprocessesviathesaerssystem AT ronankcarroll thesmallproteinscrainfluencesstaphylococcusaureusvirulencerelatedprocessesviathesaerssystem AT marcusawittekind smallproteinscrainfluencesstaphylococcusaureusvirulencerelatedprocessesviathesaerssystem AT paulbriaud smallproteinscrainfluencesstaphylococcusaureusvirulencerelatedprocessesviathesaerssystem AT jayannalsmith smallproteinscrainfluencesstaphylococcusaureusvirulencerelatedprocessesviathesaerssystem AT juliartennant smallproteinscrainfluencesstaphylococcusaureusvirulencerelatedprocessesviathesaerssystem AT ronankcarroll smallproteinscrainfluencesstaphylococcusaureusvirulencerelatedprocessesviathesaerssystem |