Panton-Valentine Leukocidin Enhances the Severity of Community-Associated Methicillin-Resistant Staphylococcus aureus Rabbit Osteomyelitis

被引:90
作者
Cremieux, Anne-Claude
Dumitrescu, Oana
Lina, Gerard
Vallee, Christian
Cote, Jean-Francois
Muffat-Joly, Martine
Lilin, Thomas
Etienne, Jerome
Vandenesch, Francois
Saleh-Mghir, Azzam
机构
[1] Département de Médecine Aigüe, Hôpital Universitaire Raymond Poincaré, Assistance Publique-Hôpitaux de Paris, Garches
[2] Faculté de Médecine Paris-Ile-de-France Ouest, Université Versailles Saint Quentin, Versailles
[3] Inserm U851, Centre National de Référence des Staphylocoques, Université Lyon 1, Lyon
[4] Service de Radiologie, Hôpital Universitaire Raymond Poincaré, Asistance Publique-Hôpitaux de Paris, Garches
[5] Service Anatomie Pathologique, Hôpital Ambroise Paré, Boulogne-Billancourt
[6] Inserm IFR2-Centre d'Explorations Fonctionnelles Intégré, UFR de Médecine Paris 7, Bichat, Paris
[7] Centre de Recherches Biomédicales, Ecole Nationale Vétérinaire d'Alfort, Maisons Alfort
来源
PLOS ONE | 2009年 / 4卷 / 09期
关键词
D O I
10.1371/journal.pone.0007204
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. Methodology/Principal Findings: 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 (LAC Delta pvl), using a low and a high inoculum (8610 5 and 4 x 10(8) CFU). With the low inoculum, bone infection was less frequent on day 7 (D7) and day 28 (D28) with LACDpvl 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 LACDpvl 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 LAC Delta pvl-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/Significance: 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.
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