Comparison of virulence in community-associated methicillin-resistant Staphylococcus aureus pulsotypes USA300 and USA400 in a rat model of pneumonia.
BACKGROUND
The predominant genetic background of community-associated methicillin-resistant Staphylococcus aureus has transitioned from USA400 to USA300 in most US communities. The explanation for this shift is unclear. We hypothesized that USA300 must be more pathogenic--specifically, that USA300 would have increased virulence when compared with USA400 in an animal model.


METHODS
Rats were inoculated intratracheally with 1 of 6 S. aureus isolates from the USA300 and USA400 backgrounds. We assessed mortality, in vivo bacterial growth, and histopathology. We assessed the in vitro expression of capsule and of selected genes believed to be important in virulence in S. aureus, including agr, saeRS, sarA, alpha-toxin (hla), and Panton-Valentine leukocidin (pvl).


RESULTS
USA300 isolates were more lethal, produced more severe pneumonia, and had higher in vivo bacterial density in the lung than did USA400 isolates. In vitro expression of agr, saeRS, sarA, hla, and pvl were greater in USA300 isolates. USA300 isolates were unencapsulated, whereas 2 of 3 USA400 isolates produced capsule.


CONCLUSIONS
USA300 isolates were more virulent than USA400 isolates in a model of necrotizing pneumonia. The explanation for this is unclear, but it likely results from increased expression of S. aureus regulatory systems (e.g., agr, saeRS, and sarA) and the resultant upregulation of key virulence factors including alpha-toxin and PVL.
Montgomery
Christopher P
CP
Department of Pediatrics, Section of Critical Care Medicine, University of Chicago, Illinois 60637, USA. cmontgomery@bsd.uchicago.edu
Boyle-Vavra
Susan
S
Adem
Patricia V
PV
Lee
Jean C
JC
Husain
Aliya N
AN
Clasen
Julia
J
Daum
Robert S
RS
D000818:Animals; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000235:genetics*; D017714:Community-Acquired Infections / Q000453:epidemiology / Q000382:microbiology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005098:Exotoxins / Q000096:biosynthesis; D007956:Leukocidins / Q000096:biosynthesis; D016106:Methicillin Resistance; D011023:Pneumonia, Staphylococcal / Q000503:physiopathology; D051381:Rats; D013203:Staphylococcal Infections / Q000453:epidemiology / Q000382:microbiology* / Q000503:physiopathology; D013211:Staphylococcus aureus / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D014774:Virulence; D037521:Virulence Factors
D001427:Bacterial Toxins; D005098:Exotoxins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; D037521:Virulence Factors