Virulence determinants associated with the Asian community-associated methicillin-resistant Staphylococcus aureus lineage ST59.
Virulence determinants associated with the Asian community-associated methicillin-resistant Staphylococcus aureus lineage ST59.
复制标题
与亚洲社区相关的耐甲氧西林金黄色葡萄球菌谱系 ST59 相关的毒力决定因素。
DOI：
10.1038/srep27899
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发表时间：
2016-06-14
影响因子：
4.6
通讯作者：
Otto M
中科院分区：
文献类型：
--
作者：
Li M;Dai Y;Zhu Y;Fu CL;Tan VY;Wang Y;Wang X;Hong X;Liu Q;Li T;Qin J;Ma X;Fang J;Otto M
了解毒力对于开发针对社区相关甲氧西林耐药金黄色葡萄球菌(CA-MRSA)感染的新疗法至关重要。CA-MRSA在美国造成持续流行，并在全球范围内呈上升趋势。然而，是什么定义了毒力，特别是全球CA-MRSA谱系的毒力，人们却知之甚少。亚洲占主导地位的CA-MRSA谱系ST59威胁着巨大的人口，具有重要的流行病学意义。然而，到目前为止，还没有使用该谱系中确定的毒力基因缺失突变体进行分子分析。在这里，我们比较了ST59 CA-MRSA分离株与地理位置匹配的医院相关MRSA分离株在皮肤、肺和血液感染模型中的毒力。根据毒素表达和毒力特性，筛选出一株具有代表性的CA-MRSA分离株，并在该分离株中获得了重要毒力决定基因(α-毒素、PsM-α、agr)的同源基因缺失突变体，用于体外和体内分析。我们的结果表明，ST59 CA-MRSA的毒力比医院相关的谱系强，支持了CA-MRSA的特征是毒力增强的观点。此外，它们显示了agr、α毒素和psmα在ST59CA-MRSA皮肤、肺和血液感染的发病机制中的强大和显著的贡献，强调了针对这些毒力决定因素的药物开发努力的价值。
Understanding virulence is vital for the development of novel therapeutics to target infections with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), which cause an ongoing epidemic in the United States and are on a global rise. However, what defines virulence particularly of global CA-MRSA lineages is poorly understood. Threatening a vast population, the predominant Asian CA-MRSA lineage ST59 is of major epidemiological importance. However, there have been no molecular analyses using defined virulence gene deletion mutants in that lineage as of yet. Here, we compared virulence in skin, lung, and blood infection models of ST59 CA-MRSA isolates with geographically matched hospital-associated MRSA isolates. We selected a representative ST59 CA-MRSA isolate based on toxin expression and virulence characteristics, and produced isogenic gene deletion mutants of important CA-MRSA virulence determinants (α-toxin, PSM α, Agr) in that isolate for in-vitro and in-vivo analyses. Our results demonstrate strongly enhanced virulence of ST59 CA-MRSA over hospital-associated lineages, supporting the notion that enhanced virulence is characteristic for CA-MRSA. Furthermore, they show strong and significant contribution of Agr, α-toxin, and PSMα to pathogenesis of ST59 CA-MRSA skin, lung, and blood infection, emphasizing the value of drug development efforts targeted toward those virulence determinants.