Is Panton-Valentine Leukocidin the Major Virulence Determinant in Community-Associated Methicillin-Resistant Staphylococcus Aureus Disease?

J Infect Dis. 2006 Dec 15;194(12):1761-70. doi: 10.1086/509506. Epub 2006 Nov 2.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) remains a major problem in hospitals, and it is now spreading in the community. A single toxin, Panton-Valentine leukocidin (PVL), has been linked by epidemiological studies to community-associated MRSA (CA-MRSA) disease. However, the role that PVL plays in the pathogenesis of CA-MRSA has not been tested directly. To that end, we used mouse infection models to compare the virulence of PVL-positive with that of PVL-negative CA-MRSA representing the leading disease-causing strains. Unexpectedly, strains lacking PVL were as virulent in mouse sepsis and abscess models as those containing the leukotoxin. Isogenic PVL-negative (lukS/F-PV knockout) strains of USA300 and USA400 were as lethal as wild-type strains in a sepsis model, and they caused comparable skin disease. Moreover, lysis of human neutrophils and pathogen survival after phagocytosis were similar between wild-type and mutant strains. Although the toxin may be a highly linked epidemiological marker for CA-MRSA strains, we conclude that PVL is not the major virulence determinant of CA-MRSA.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abscess / microbiology
  • Animals
  • Animals, Outbred Strains
  • Bacterial Toxins / genetics
  • Bacterial Toxins / metabolism
  • Exotoxins / genetics
  • Exotoxins / metabolism
  • Exotoxins / physiology*
  • Female
  • Humans
  • Immunocompetence
  • Leukocidins / genetics
  • Leukocidins / metabolism
  • Leukocidins / physiology*
  • Leukocytes, Mononuclear / microbiology
  • Methicillin / pharmacology
  • Methicillin Resistance
  • Mice
  • Mice, Hairless
  • Neutrophils / microbiology
  • Point Mutation
  • Sepsis / microbiology
  • Staphylococcal Infections / microbiology*
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / growth & development
  • Staphylococcus aureus / metabolism
  • Staphylococcus aureus / pathogenicity*
  • Virulence

Substances

  • Bacterial Toxins
  • Exotoxins
  • Leukocidins
  • Panton-Valentine leukocidin
  • Methicillin