Panton-valentine leukocidin enhances the severity of community-associated methicillin-resistant Staphylococcus aureus rabbit osteomyelitis.
BACKGROUND
Extensive spread of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in the United States, and the concomitant increase in severe invasive staphylococcal infections, including osteomyelitis, in healthy children, has led to renewed interest in Panton-Valentine leukocidin (PVL). However, the pathogenetic role of PVL in staphylococcal infections remains controversial, possibly because it depends on the site of infection.


RESULTS
We compared the course of experimental rabbit osteomyelitis due to the PVL-positive CA-MRSA strain USA 300 (LAC) and its PVL-negative isogenic derivative (LACDeltapvl), using a low and a high inoculum (8x10(5) and 4x10(8) CFU). With the low inoculum, bone infection was less frequent on day 7 (D7) and day 28 (D28) with LACDeltapvl than with LAC (respectively 12/19 and 18/19 animals, p = 0.042). With the high inoculum of both strains, all the animals were infected on D7 and the infection persisted on D28 in almost every case. However, tibial bacterial counts and the serum CRP concentration fell significantly between D7 and D28 with LACDeltapvl but not with LAC. Respectively 67% and 60% of LAC-infected rabbits had bone deformation and muscle/joint involvement on D7, compared to 0% and 7% of LACDeltapvl-infected rabbits (p = 0.001 and p = 0.005 respectively). Between D0 and D28, the anti-PVL antibody titer increased significantly only with the high inoculum of LAC.


CONCLUSIONS
PVL appears to play a role in the persistence and rapid local extension of rabbit osteomyelitis, in keeping with the greater severity of human bone infections due to PVL-positive S. aureus. The possible therapeutic implications of these findings are discussed.
Département de médecine aigüe, Hôpital Universitaire Raymond Poincaré, Assistance Publique-Hôpitaux de Paris, Garches, France.
Anne-Claude
AC
Crémieux
Oana
O
Dumitrescu
Gerard
G
Lina
Christian
C
Vallee
Jean-François
JF
Côté
Martine
M
Muffat-Joly
Thomas
T
Lilin
Jerome
J
Etienne
François
F
Vandenesch
Azzam
A
Saleh-Mghir
D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry; D001842:Bone and Bones / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D004195:Disease Models, Animal; D005098:Exotoxins / Q000737:chemistry / Q000502:physiology*; D005260:Female; D006801:Humans; D007956:Leukocidins / Q000737:chemistry / Q000502:physiology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000378:metabolism*; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D010019:Osteomyelitis / Q000378:metabolism*; D011817:Rabbits; D013203:Staphylococcal Infections / Q000453:epidemiology* / Q000382:microbiology; D037521:Virulence Factors / Q000378:metabolism
D001427:Bacterial Toxins; D005098:Exotoxins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; D037521:Virulence Factors; D002097:C-Reactive Protein