Contribution of Panton-Valentine leukocidin in community-associated methicillin-resistant Staphylococcus aureus pathogenesis

• Published in: PloS one Vol. 3; no. 9; p. e3198
• Main Authors: Diep, Binh An, Palazzolo-Ballance, Amy M, Tattevin, Pierre, Basuino, Li, Braughton, Kevin R, Whitney, Adeline R, Chen, Liang, Kreiswirth, Barry N, Otto, Michael, DeLeo, Frank R, Chambers, Henry F
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12-09-2008; Public Library of Science (PLoS)
• Subjects: Analysis; Animal species; Animals; Bacteremia; Bacteremia - diagnosis; Bacteremia - metabolism; Bacteria; Bacterial Toxins - metabolism; Communities; Cytokines; Dentistry; Disease Models, Animal; DNA microarrays; Drug resistance; Exotoxins - metabolism; Experimental infection; Gene Deletion; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Granulocytes; Granulocytes - cytology; Hospitals; Infectious diseases; Infectious Diseases/Bacterial Infections; Kidneys; Laboratories; Leukocidin; Leukocidins - metabolism; Leukocytes (granulocytic); Medical research; Medicine; Methicillin; Methicillin Resistance - drug effects; Methicillin Resistance - genetics; Microbial drug resistance; Microbiology; Neutrophils; Oligonucleotide Array Sequence Analysis; Pathogenesis; Pneumonia; Protein seeding; Proteins; Proteomics - methods; Public health; Public Health and Epidemiology/Infectious Diseases; Rabbits; Reverse Transcriptase Polymerase Chain Reaction; Sepsis; Staphylococcal infections; Staphylococcus aureus; Staphylococcus aureus - metabolism; Staphylococcus aureus - pathogenicity; Staphylococcus infections; Strains (organisms); Virulence Factors; San Francisco California; Montana; California; United States > US; New Jersey
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0003198

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.