Methicillin resistance reduces the virulence of healthcare-associated methicillin-resistant staphylococcus aureus by interfering with the agr quorum sensing system

Rudkin, Justine K.; Edwards, Andrew M.; Bowden, Maria G.; Brown, Eric L.; Pozzi, Clarissa; Waters, Elaine M.; Chan, Weng C.; Williams, Paul; O'Gara, James P.; Massey, Ruth C.

Abstract

The difficulty in successfully treating infections caused by methicillin-resistant Staphylococcus aureus (MRSA) has led to them being referred to as highly virulent or pathogenic. In our study of one of the major healthcare-associated MRSA (HA-MRSA) clones, we show that expression of the gene responsible for conferring methicillin resistance (mecA) is also directly responsible for reducing the ability of HA-MRSA to secrete cytolytic toxins. We show that resistance to methicillin induces changes in the cell wall, which affects the bacteria's agr quorum sensing system. This leads to reduced toxin expression and, as a consequence, reduced virulence in a murine model of sepsis. This diminished capacity to cause infection may explain the inability of HA-MRSA to move into the community and help us understand the recent emergence of community-associated MRSA (CA-MRSA). CA-MRSA typically express less penicillin-binding protein 2a (encoded by mecA), allowing them to maintain full virulence and succeed in the community environment. © 2012 The Author. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

Citation

Rudkin, J. K., Edwards, A. M., Bowden, M. G., Brown, E. L., Pozzi, C., Waters, E. M., Chan, W. C., Williams, P., O'Gara, J. P., & Massey, R. C. (2012). Methicillin resistance reduces the virulence of healthcare-associated methicillin-resistant staphylococcus aureus by interfering with the agr quorum sensing system. Journal of Infectious Diseases, 205(5), 798-806. https://doi.org/10.1093/infdis/jir845

• Journal Article Type: Article
• Acceptance Date: Oct 14, 2011
• Online Publication Date: Mar 1, 2012
• Publication Date: Mar 1, 2012
• Deposit Date: Sep 10, 2020
• Publicly Available Date: Sep 11, 2020
• Journal: Journal of Infectious Diseases
• Print ISSN: 0022-1899
• Electronic ISSN: 1537-6613
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 205
• Issue: 5
• Pages: 798-806
• DOI: https://doi.org/10.1093/infdis/jir845
• Public URL: https://nottingham-repository.worktribe.com/output/3104863
• Publisher URL: https://academic.oup.com/jid/article/205/5/798/839668