Methicillin Resistance Reduces the Virulence of Healthcare-Associated Methicillin-Resistant Staphylococcus aureus by Interfering With the agr Quorum Sensing System

Justine K Rudkin, Andrew M Edwards, M G Bowden, E L Brown, C Pozzi, E M Waters, W C Chan, P Williams, J P O'Gara, Ruth C Massey

Research output: Contribution to journalArticle

81 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)798-806
Number of pages9
JournalJournal of Infectious Diseases
Volume205
Issue number5
DOIs
Publication statusPublished - 2012

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Quorum Sensing
Methicillin Resistance
Methicillin-Resistant Staphylococcus aureus
Virulence
Delivery of Health Care
Penicillin-Binding Proteins
Infection
Cell Wall
Sepsis
Clone Cells
Bacteria
Gene Expression

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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, M G; Brown, E L; Pozzi, C; Waters, E M; Chan, W C; Williams, P; O'Gara, J P; Massey, Ruth C.

In: Journal of Infectious Diseases, Vol. 205, No. 5, 2012, p. 798-806.

Research output: Contribution to journalArticle

Rudkin, JK, Edwards, AM, Bowden, MG, Brown, EL, Pozzi, C, Waters, EM, Chan, WC, Williams, P, O'Gara, JP & Massey, RC 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, vol. 205, no. 5, pp. 798-806. https://doi.org/10.1093/infdis/jir845
Rudkin, Justine K ; Edwards, Andrew M ; Bowden, M G ; Brown, E L ; Pozzi, C ; Waters, E M ; Chan, W C ; Williams, P ; O'Gara, J P ; Massey, Ruth C. / Methicillin Resistance Reduces the Virulence of Healthcare-Associated Methicillin-Resistant Staphylococcus aureus by Interfering With the agr Quorum Sensing System. In: Journal of Infectious Diseases. 2012 ; Vol. 205, No. 5. pp. 798-806.
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