Virulence determinants of community-acquired methicillin-resistant Staphylococcus aureus
- Franklin D Lowy, MD
Franklin D Lowy, MD
- Professor of Medicine and Pathology & Cell Biology (in Epidemiology)
- Columbia University, College of Physicians and Surgeons
The virulence and rapid transmission of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have raised interest in understanding the pathogenesis of this organism . The most prevalent strain in the United States, USA300, is now among the most common causes of skin and soft tissue infections in urban emergency departments across the United States [2,3]. Up to 10 percent of these infections are invasive infections such as sepsis, meningitis, osteomyelitis, and necrotizing pneumonia [4,5].
Issues related to evolution and virulence determinants that appear to be specific to the emergence of these epidemic CA-MRSA clones will be reviewed here. Issues related to the microbiology of MRSA are discussed in detail separately. (See "Methicillin-resistant Staphylococcus aureus (MRSA): Microbiology".)
EVOLUTION OF CA-MRSA
Several of the emergent community-acquired methicillin-resistant S. aureus (CA-MRSA) strain sequences demonstrate striking similarity to other clonal MRSA strains [6,7]. The genetic persistence of these strains over time suggests they have core genomic determinants that facilitate their survival and virulence. A limited number of clones are responsible for most MRSA infections. The original methicillin-resistant isolate is strikingly similar in nucleotide sequence to the epidemic strain USA300 . In addition, the southwest Pacific strain that has caused infections in Australia and other countries in the region is a descendent of the phage 80/81 strain that has caused outbreaks in newborn nurseries in the 1960s .
The genetic sequence of USA300 revealed that these strains contained a unique mobile element that includes the methicillin-resistance gene staphylococcal cassette chromosome mec (SCCmec) IVa, the arginine catabolic mobile element, enterotoxins Seq and Sek, and a prophage containing the leukocidin, Panton-Valentine leukocidin .
VIRULENCE DETERMINANTS AND THEIR REGULATION
The enhanced virulence of the community-acquired methicillin-resistant S. aureus (CA-MRSA) strains is not fully understood but appears to result from several contributing factors (figure 1), including:
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- EVOLUTION OF CA-MRSA
- VIRULENCE DETERMINANTS AND THEIR REGULATION
- Panton-Valentine leukocidin
- Phenol soluble modulins (PSMs)
- Arginine catabolic mobile element (ACME)
- Accessory gene regulator
- Serologic response to infection
- Transmission and survival in the environment