title: Lack of a major role of Staphylococcus aureus Panton-Valentine leukocidin in lower respiratory tract infection in nonhuman primates.
abstract: Panton-Valentine leukocidin (PVL) is a two-component cytolytic toxin epidemiologically linked to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, including serious invasive infections caused by the epidemic clone referred to as strain USA300. Although PVL has long been known to be a S. aureus virulence molecule in vitro, the relative contribution of this leukotoxin to invasive CA-MRSA infections such as pneumonia remains controversial. We developed a nonhuman primate model of CA-MRSA pneumonia and used it to test the hypothesis that PVL contributes to lower respiratory tract infections caused by S. aureus strain USA300. The lower respiratory tract disease observed in this monkey model mimicked the clinical and pathological features of early mild to moderate S. aureus pneumonia in humans, including fine-structure histopathology. In this experiment using a large sample of monkeys and multiple time points of examination, no involvement of PVL in virulence could be detected. Compared with the wild-type parental USA300 strain, the isogenic PVL deletion-mutant strain caused equivalent lower respiratory tract pathology. We conclude that PVL does not contribute to lower respiratory tract infection in this nonhuman primate model of human CA-MRSA pneumonia.
authors.affiliation: Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, the Methodist Hospital, and University of Houston, B490, 6565 Fannin Street, Houston, TX 77030, USA.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Olsen
authors.forename: Scott D
authors.initials: SD
authors.lastname: Kobayashi
authors.forename: Ara A
authors.initials: AA
authors.lastname: Ayeras
authors.forename: Madiha
authors.initials: M
authors.lastname: Ashraf
authors.forename: Shawna F
authors.initials: SF
authors.lastname: Graves
authors.forename: Willie
authors.initials: W
authors.lastname: Ragasa
authors.forename: Tammy
authors.initials: T
authors.lastname: Humbird
authors.forename: Jamieson L
authors.initials: JL
authors.lastname: Greaver
authors.forename: Constance
authors.initials: C
authors.lastname: Cantu
authors.forename: Jody L
authors.initials: JL
authors.lastname: Swain
authors.forename: Leslie
authors.initials: L
authors.lastname: Jenkins
authors.forename: Terry
authors.initials: T
authors.lastname: Blasdel
authors.forename: Philip T
authors.initials: PT
authors.lastname: Cagle
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Gardner
authors.forename: Frank R
authors.initials: FR
authors.lastname: DeLeo
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D016207:Cytokines / Q000097:blood; D005098:Exotoxins / Q000633:toxicity*; D007956:Leukocidins / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008252:Macaca fascicularis / Q000382:microbiology; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000502:physiology; D008828:Microbiological Techniques; D011651:Pulmonary Artery / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D012141:Respiratory Tract Infections / Q000097:blood / Q000150:complications* / Q000382:microbiology* / Q000473:pathology; D013203:Staphylococcal Infections / Q000097:blood / Q000150:complications* / Q000382:microbiology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000187:drug effects
chemical_list: D000209:Acute-Phase Proteins; D001427:Bacterial Toxins; D016207:Cytokines; D005098:Exotoxins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin