title: Is Panton-Valentine leukocidin the major virulence determinant in community-associated methicillin-resistant Staphylococcus aureus disease?
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.
authors.affiliation: Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
authors.forename: Jovanka M
authors.initials: JM
authors.lastname: Voyich
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
authors.forename: Barun
authors.initials: B
authors.lastname: Mathema
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Braughton
authors.forename: Adeline R
authors.initials: AR
authors.lastname: Whitney
authors.forename: Diane
authors.initials: D
authors.lastname: Welty
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Long
authors.forename: David W
authors.initials: DW
authors.lastname: Dorward
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Gardner
authors.forename: Gérard
authors.initials: G
authors.lastname: Lina
authors.forename: Barry N
authors.initials: BN
authors.lastname: Kreiswirth
authors.forename: Frank R
authors.initials: FR
authors.lastname: DeLeo
mesh_terms: D000038:Abscess / Q000382:microbiology; D000818:Animals; D021461:Animals, Outbred Strains; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D005098:Exotoxins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D007121:Immunocompetence; D007956:Leukocidins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D008712:Methicillin / Q000494:pharmacology; D016106:Methicillin Resistance; D051379:Mice; D008812:Mice, Hairless; D009504:Neutrophils / Q000382:microbiology; D017354:Point Mutation; D018805:Sepsis / Q000382:microbiology; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001427:Bacterial Toxins; D005098:Exotoxins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; D008712:Methicillin