Staphylococcus aureus Panton-Valentine leukocidin contributes to inflammation and muscle tissue injury.
Staphylococcus aureus Panton-Valentine leukocidin contributes to inflammation and muscle tissue injury.
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DOI：
10.1371/journal.pone.0006387
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发表时间：
2009-07-27
期刊：
影响因子：
3.7
通讯作者：
Liu GY
中科院分区：
文献类型：
--
作者：
Tseng CW;Kyme P;Low J;Rocha MA;Alsabeh R;Miller LG;Otto M;Arditi M;Diep BA;Nizet V;Doherty TM;Beenhouwer DO;Liu GY
社区相关耐甲氧西林金黄色葡萄球菌(CA-MRSA)危害全球公共卫生，流行病学资料表明，大多数CA-MRSA菌株表达的白血球蛋白(PVL)可导致严重的人类感染，尤其是在年轻和免疫能力强的宿主中。PVL被认为可以诱导吞噬细胞的细胞溶解或凋亡。然而，最近对有无PVL的同基因CA-MRSA菌株的比较显示，在人PMN杀伤活性方面没有差异。此外，迄今为止进行的许多小鼠研究都未能证明PVL的毒力作用，从而引发了这样一个问题：PVL在人类感染中是否具有机械性作用？在这篇报告中，我们评估了PVL在严重皮肤和软组织感染中的作用。我们从坏死性筋膜炎患者分离的CA-MRSA菌株中产生PVL突变株，并使用这些工具评估PVL在体内的致病作用。在坏死性软组织感染模型中，我们发现PVL对肌肉有明显的损伤，但对皮肤没有影响。肌肉损伤与促炎趋化因子KC、MIP-2和RANTES的诱导以及中性粒细胞的募集有关。组织损伤在年轻小鼠和那些更有效地清除金黄色葡萄球菌的小鼠中最为突出，而在对这种病原体的免疫反应较有限的老年小鼠和小鼠品系中不明显。PVL介导的损伤可被抗PVL抗体阻断。我们的数据为CA-MRSA的发病机制、流行病学和治疗提供了新的见解。PVL可增加CA-MRSA感染后肌炎的发生率，该毒素可能通过直接杀伤吞噬细胞以外的机制介导组织损伤。
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) threatens public health worldwide, and epidemiologic data suggest that the Panton-Valentine Leukocidin (PVL) expressed by most CA-MRSA strains could contribute to severe human infections, particularly in young and immunocompetent hosts. PVL is proposed to induce cytolysis or apoptosis of phagocytes. However, recent comparisons of isogenic CA-MRSA strains with or without PVL have revealed no differences in human PMN cytolytic activity. Furthermore, many of the mouse studies performed to date have failed to demonstrate a virulence role for PVL, thereby provoking the question: does PVL have a mechanistic role in human infection? In this report, we evaluated the contribution of PVL to severe skin and soft tissue infection. We generated PVL mutants in CA-MRSA strains isolated from patients with necrotizing fasciitis and used these tools to evaluate the pathogenic role of PVL in vivo. In a model of necrotizing soft tissue infection, we found PVL caused significant damage of muscle but not the skin. Muscle injury was linked to induction of pro-inflammatory chemokines KC, MIP-2, and RANTES, and recruitment of neutrophils. Tissue damage was most prominent in young mice and in those strains of mice that more effectively cleared S. aureus, and was not significant in older mice and mouse strains that had a more limited immune response to the pathogen. PVL mediated injury could be blocked by pretreatment with anti-PVL antibodies. Our data provide new insights into CA-MRSA pathogenesis, epidemiology and therapeutics. PVL could contribute to the increased incidence of myositis in CA-MRSA infection, and the toxin could mediate tissue injury by mechanisms other than direct killing of phagocytes.
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影响因子：
64.8
作者：
Kash, John C.;Tumpey, Terrence M.;Katze, Michael G.
通讯作者：
Katze, Michael G.
影响因子：
8
作者：
Bocchini, CE;Hulten, KG;Kaplan, SL
通讯作者：
Kaplan, SL
影响因子：
158.5
作者：
Miller, LG;Perdreau-Remington, F;Spellberg, B
通讯作者：
Spellberg, B
DOI：
10.1111/j.1469-0691.2008.02648.x
发表时间：
2009-02
期刊：
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
影响因子：
--
作者：
Brown EL;Dumitrescu O;Thomas D;Badiou C;Koers EM;Choudhury P;Vazquez V;Etienne J;Lina G;Vandenesch F;Bowden MG
通讯作者：
Bowden MG
影响因子：
4.4
作者：
Ginaldi, L;De Martinis, M;Quaglino, D
通讯作者：
Quaglino, D