Lack of a major role of Staphylococcus aureus Panton-Valentine leukocidin in lower respiratory tract infection in nonhuman primates.
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.
Olsen
Randall J
RJ
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.
Kobayashi
Scott D
SD
Ayeras
Ara A
AA
Ashraf
Madiha
M
Graves
Shawna F
SF
Ragasa
Willie
W
Humbird
Tammy
T
Greaver
Jamieson L
JL
Cantu
Constance
C
Swain
Jody L
JL
Jenkins
Leslie
L
Blasdel
Terry
T
Cagle
Philip T
PT
Gardner
Donald J
DJ
DeLeo
Frank R
FR
Musser
James M
JM
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
D000209:Acute-Phase Proteins; D001427:Bacterial Toxins; D016207:Cytokines; D005098:Exotoxins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin