Panton-Valentine Leukocidin
Abstract & Commentary
By Robert Muder, MD, Hospital Epidemiologist, Pittsburgh VA Medical Center, Section Editor, Hospital Epidemiology, is Associate Editor for Infectious Disease Alert.
Dr. Muder does research for Aventis and Pharmacia.
Synopsis: Although most strains of community associated MRSA possess the Panton-Valentine leukocidin, this exotoxin does appear to be a major virulence determinant.
Source: Voyich JM, et al. Is Panton-Valentine leukocidin the major virulence determinant in community-associated methicillin-resistant Staphylococcus aureus disease? J Infect Dis. 2006;194:1761-1770.
Community-Associated MRSA (CA-MRSA) has emerged as an important cause of skin and soft-tissue infection.1 Most isolates of CA-MRSA are positive for the Panton-Valentine leukocidin (PVL), an exotoxin that is generally absent from "classic" hospital-associated MRSA strains.2 This suggests that PVL may be an important virulence determinant in CA-MRSA.
Voyich and colleagues used a mouse infection model to compare virulence among representative PVL+ and PVL- strains of S. aureus. There were no significant differences between PVL+ and PVL-stains in virulence, as measured by survival after induction of sepsis, as well as cutaneous abscess volume or severity of dermal necrosis in a skin-infection model. Isogenic PVL-strains of USA300 and USA400 were identical in virulence to wild type strains in the sepsis and skin-infection mouse models. In addition, the mutant strains were as toxic to human neutrophils as the wild type strains as measured by neutrophil lysis and bacterial survival after phagocytosis.
Commentary
CA-MRSA strains are genetically distinct from "classic" hospital-associated MRSA strains. Methicillin resistance is caused by a distinct methicillin resistance gene cassette, SCC mecIV. Most CA-MRSA in the United States isolates belong to 1 of 2 distinct clonal types, designated USA300 and USA400. The majority of CA-MRSA isolates have produced PVL, an exotoxin that is highly toxic to human neutrophils. This has led to speculation that PVL is an important virulence factor in CA-MRSA, and may be responsible for the occurrence of unusually severe soft-tissue infections, and, less commonly, severe pulmonary infections associated with CA-MRSA.
Voyich and colleagues present rather convincing evidence that PVL is not primarily responsible for the observed virulence of CA-MRSA. The most convincing evidence is that mutant CA-MRSA strains negative for PVL, but otherwise genetically identical to wild type strains, are fully virulent in mice, and just as toxic to human neutrophils. Thus, PVL has been demoted from a major virulence determinant to an epidemiologic marker. The genetic basis for the virulence of CA-MRSA remains to be determined.
References:
- Fridkin SK, et al. Methicillin-resistant Staphylococcus aureus disease in three communities. N Engl J Med. 2005;352:1436-1444.
- Rybak MJ, LaPlante KL. Community-associated methicillin-resistant Staphylococcus aureus: a review. Pharmacotherapy. 2005;25:74-85.
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