title: Contribution of Panton-Valentine leukocidin in community-associated methicillin-resistant Staphylococcus aureus pathogenesis.
abstract: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains typically carry genes encoding Panton-Valentine leukocidin (PVL). We used wild-type parental and isogenic PVL-deletion (Delta pvl) strains of USA300 (LAC and SF8300) and USA400 (MW2) to test whether PVL alters global gene regulatory networks and contributes to pathogenesis of bacteremia, a hallmark feature of invasive staphylococcal disease. Microarray and proteomic analyses revealed that PVL does not alter gene or protein expression, thereby demonstrating that any contribution of PVL to CA-MRSA pathogenesis is not mediated through interference of global gene regulatory networks. Inasmuch as a direct role for PVL in CA-MRSA pathogenesis remains to be determined, we developed a rabbit bacteremia model of CA-MRSA infection to evaluate the effects of PVL. Following experimental infection of rabbits, an animal species whose granulocytes are more sensitive to the effects of PVL compared with the mouse, we found a contribution of PVL to pathogenesis over the time course of bacteremia. At 24 and 48 hours post infection, PVL appears to play a modest, but measurable role in pathogenesis during the early stages of bacteremic seeding of the kidney, the target organ from which bacteria were not cleared. However, the early survival advantage of this USA300 strain conferred by PVL was lost by 72 hours post infection. These data are consistent with the clinical presentation of rapid-onset, fulminant infection that has been associated with PVL-positive CA-MRSA strains. Taken together, our data indicate a modest and transient positive effect of PVL in the acute phase of bacteremia, thereby providing evidence that PVL contributes to CA-MRSA pathogenesis.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Binh An
authors.initials: BA
authors.lastname: Diep
authors.forename: Amy M
authors.initials: AM
authors.lastname: Palazzolo-Ballance
authors.forename: Pierre
authors.initials: P
authors.lastname: Tattevin
authors.forename: Li
authors.initials: L
authors.lastname: Basuino
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Braughton
authors.forename: Adeline R
authors.initials: AR
authors.lastname: Whitney
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Barry N
authors.initials: BN
authors.lastname: Kreiswirth
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
authors.forename: Frank R
authors.initials: FR
authors.lastname: DeLeo
authors.forename: Henry F
authors.initials: HF
authors.lastname: Chambers
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000175:diagnosis / Q000378:metabolism; D001427:Bacterial Toxins / Q000378:metabolism*; D004195:Disease Models, Animal; D005098:Exotoxins / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006098:Granulocytes / Q000166:cytology; D007956:Leukocidins / Q000378:metabolism*; D016106:Methicillin Resistance / Q000187:drug effects / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D040901:Proteomics / Q000379:methods; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000378:metabolism* / Q000472:pathogenicity; D037521:Virulence Factors
chemical_list: D001427:Bacterial Toxins; D005098:Exotoxins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; D037521:Virulence Factors
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