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Importance of the Global Regulators Agr and SaeRS in the Pathogenesis of CA-MRSA USA300 Infection
Open accessAbstract
CA-MRSA infection, driven by the emergence of the USA300 genetic background, has become epidemic in the United States. USA300 isolates are hypervirulent, compared with other CA- and HA-MRSA strains, in experimental models of necrotizing pneumonia and skin infection. Interestingly, USA300 isolates also have increased expression of core genomic global regulatory and virulence factor genes, including agr and saeRS. To test the hypothesis that agr and saeRS promote the observed hypervirulent phenotype of USA300, isogenic deletion mutants of each were constructed in USA300. The effects of gene deletion on expression and protein abundance of selected downstream virulence genes were assessed by semiquantitative real-time reverse-transcriptase PCR (qRT-PCR) and western blot, respectively. The effects of gene deletion were also assessed in mouse models of necrotizing pneumonia and skin infection. Deletion of saeRS, and, to a lesser extent, agr, resulted in attenuated expression of the genes encoding α-hemolysin (hla) and the Panton-Valentine leukocidin (lukSF-PV). Despite the differences in hla transcription, the toxin was undetectable in culture supernatants of either of the deletion mutants. Deletion of agr, but not saeRS, markedly increased the expression of the gene encoding protein A (spa), which correlated with increased protein abundance. Each deletion mutant demonstrated significant attenuation of virulence, compared with wild-type USA300, in mouse models of necrotizing pneumonia and skin infection. We conclude that agr and saeRS each independently contribute to the remarkable virulence of USA300, likely by means of their effects on expression of secreted toxins.
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Poring over pores: α-hemolysin and Panton-Valentine leukocidin in Staphylococcus aureus pneumonia
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Staphylococcus aureus protein A induces airway epithelial inflammatory responses by activating TNFR1
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Evolution of virulence in epidemic community-associated methicillin-resistant Staphylococcus aureus
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“The quality and quantity of RNA were assessed by A260/A280 and by visualization on a 1.2% formaldehyde-agarose gel. qRT-PCR.”
InfluentialDiep, B. A., Chan, L., Tattevin, P., Kajikawa, O., Martin, T. R., Basuino, L., Mai, T. T., Marbach, H., Braughton, K. R., Whitney, A. R., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912403107 · Cited by 347
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Cited by
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Cheung, G. Y. C., Bae, J. S., & Otto, M. (2021) · Virulence · doi:10.1080/21505594.2021.1878688 · Cited by 1,380
Regulation of Staphylococcus aureus Virulence
Jenul, C., & Horswill, A. R. (2019) · Microbiology Spectrum · doi:10.1128/microbiolspec.gpp3-0031-2018 · Cited by 549
Quorum-sensing regulation in staphylococci—an overview
Le, K. Y., & Otto, M. (2015) · Frontiers in Microbiology · doi:10.3389/fmicb.2015.01174 · Cited by 490
The Bicomponent Pore-Forming Leucocidins of Staphylococcus aureus
Alonzo, F., & Torres, V. J. (2014) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00055-13 · Cited by 276
Metadata
- Authors
- Montgomery, C. P., Boyle-Vavra, S., & Daum, R. S.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-12-02
- Volume
- 5
- Issue
- 12
- Pages
- e15177
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W1963912540
- Cited by
- 199
- References
- 9
- FWCI
- 7.49
- Type
- journal article
- Language
- en
- Open access
- gold
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