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

J Infect Dis. 2012 Mar 1;205(5):798-806. doi: 10.1093/infdis/jir845. Epub 2012 Feb 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / drug effects
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Bacterial Proteins / pharmacology
  • Bacterial Toxins / metabolism*
  • Cell Survival
  • Cell Wall / metabolism
  • Cross Infection
  • Disease Models, Animal
  • Gene Expression
  • Methicillin Resistance / genetics*
  • Methicillin-Resistant Staphylococcus aureus / genetics*
  • Methicillin-Resistant Staphylococcus aureus / metabolism
  • Methicillin-Resistant Staphylococcus aureus / pathogenicity*
  • Mice
  • Penicillin-Binding Proteins / metabolism
  • Peptide Synthases / metabolism
  • Peptides, Cyclic
  • Quorum Sensing / genetics
  • Sepsis / microbiology
  • T-Lymphocytes
  • Trans-Activators / drug effects
  • Trans-Activators / genetics
  • Trans-Activators / metabolism


  • Agr protein, Staphylococcus aureus
  • AgrD protein, Staphylococcus
  • Bacterial Proteins
  • Bacterial Toxins
  • Penicillin-Binding Proteins
  • Peptides, Cyclic
  • Trans-Activators
  • mecA protein, Staphylococcus aureus
  • penicillin-binding protein 2a, Streptococcus
  • Peptide Synthases