Contribution of Panton-Valentine Leukocidin in Community-Associated Methicillin-Resistant Staphylococcus aureus Pathogenesis
Contribution of Panton-Valentine Leukocidin in Community-Associated Methicillin-Resistant Staphylococcus aureus Pathogenesis
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DOI：
10.1371/journal.pone.0003198
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发表时间：
2008-09-12
期刊：
影响因子：
3.7
通讯作者：
Chambers, Henry F.
中科院分区：
文献类型：
--
作者：
Diep, Binh An;Palazzolo-Ballance, Amy M.;Chambers, Henry F.
社区相关耐甲氧西林金黄色葡萄球菌（CA-MRSA）菌株通常携带编码Panton-Valentine杀白细胞素（PVL）的基因。我们使用USA 300（LAC和SF 8300）和USA 400（MW 2）的野生型亲本和同基因PVL缺失（Delta pvl）菌株来测试PVL是否改变全球基因调控网络并有助于菌血症的发病机制，这是侵袭性葡萄球菌疾病的标志性特征。微阵列和蛋白质组学分析显示，PVL不改变基因或蛋白质表达，从而证明PVL对CA-MRSA发病机制的任何贡献都不是通过干扰全球基因调控网络介导的。由于PVL在CA-MRSA发病机制中的直接作用仍有待确定，我们开发了CA-MRSA感染的兔菌血症模型来评估PVL的作用。实验感染兔后，与小鼠相比，其粒细胞对PVL的作用更敏感的动物物种，我们发现PVL在菌血症的时间过程中对发病机制的贡献。在感染后24和48小时，PVL似乎在肾（细菌未被清除的靶器官）的菌血症接种的早期阶段在发病机制中发挥适度但可测量的作用。然而，由PVL赋予的该USA 300菌株的早期存活优势在感染后72小时丧失。这些数据与PVL阳性CA-MRSA菌株相关的快速发作、暴发性感染的临床表现一致。综上所述，我们的数据表明PVL在菌血症急性期有适度和短暂的积极作用，从而提供了PVL有助于CA-MRSA发病机制的证据。
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains typically carry genes encoding Panton-Valentine leukocidin (PVL). We used wild-type parental and isogenic PVL-deletion (Delta pvl) strains of USA300 (LAC and SF8300) and USA400 (MW2) to test whether PVL alters global gene regulatory networks and contributes to pathogenesis of bacteremia, a hallmark feature of invasive staphylococcal disease. Microarray and proteomic analyses revealed that PVL does not alter gene or protein expression, thereby demonstrating that any contribution of PVL to CA-MRSA pathogenesis is not mediated through interference of global gene regulatory networks. Inasmuch as a direct role for PVL in CA-MRSA pathogenesis remains to be determined, we developed a rabbit bacteremia model of CA-MRSA infection to evaluate the effects of PVL. Following experimental infection of rabbits, an animal species whose granulocytes are more sensitive to the effects of PVL compared with the mouse, we found a contribution of PVL to pathogenesis over the time course of bacteremia. At 24 and 48 hours post infection, PVL appears to play a modest, but measurable role in pathogenesis during the early stages of bacteremic seeding of the kidney, the target organ from which bacteria were not cleared. However, the early survival advantage of this USA300 strain conferred by PVL was lost by 72 hours post infection. These data are consistent with the clinical presentation of rapid-onset, fulminant infection that has been associated with PVL-positive CA-MRSA strains. Taken together, our data indicate a modest and transient positive effect of PVL in the acute phase of bacteremia, thereby providing evidence that PVL contributes to CA-MRSA pathogenesis.