Panton-valentine leukocidin enhances the severity of community-associated methicillin-resistant Staphylococcus aureus rabbit osteomyelitis.

Panton-valentine leukocidin enhances the severity of community-associated methicillin-resistant Staphylococcus aureus rabbit osteomyelitis.
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DOI:
10.1371/journal.pone.0007204
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发表时间:
2009-09-25
期刊:
影响因子:
3.7
通讯作者:
Saleh-Mghir A
Saleh-Mghir A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Crémieux AC;Dumitrescu O;Lina G;Vallee C;Côté JF;Muffat-Joly M;Lilin T;Etienne J;Vandenesch F;Saleh-Mghir A

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社区相关耐甲氧西林金黄色葡萄球菌(CA-MRSA)在美国的广泛传播,以及健康儿童中严重侵袭性葡萄球菌感染(包括骨髓炎)的伴随增加,导致对Panton-Valentine杀白细胞素(PVL)的重新关注。然而,PVL在葡萄球菌感染中的致病作用仍然存在争议,可能是因为它取决于感染部位。我们使用低和高接种量(8×105和4×108 CFU)比较了由PVL阳性CA-MRSA菌株USA 300(LAC)及其PVL阴性同基因衍生物(LACΔpvl)引起的实验性兔骨髓炎的过程。在低接种量下,LACΔpvl在第7天(D 7)和第28天(D28)的骨感染频率低于LAC(分别为12/19和18/19只动物,p = 0.042)。  在两种菌株的高接种量下,所有动物均在D 7感染,并且几乎所有病例的感染持续到D28。然而,使用LACΔpvl时,胫骨细菌计数和血清CRP浓度在D 7和D28之间显著下降,而使用LAC时则没有。在D 7时,分别有67%和60%的LAC感染兔发生骨变形和肌肉/关节受累,而LACΔ pvl感染兔为0%和7%(分别为p= 0.001和p =0.005)。   在D 0和D28之间,抗PVL抗体滴度仅在高LAC接种量下显著增加。PVL似乎在兔骨髓炎的持续和快速局部扩展中起作用,与PVL阳性S.金黄色。这些研究结果可能的治疗意义进行了讨论。
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. 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 (LACΔpvl), using a low and a high inoculum (8×105 and 4×108 CFU). With the low inoculum, bone infection was less frequent on day 7 (D7) and day 28 (D28) with LACΔpvl 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 LACΔpvl 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 LACΔpvl-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. 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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