A geographic variant of the Staphylococcus aureus Panton-Valentine leukocidin toxin and the origin of community-associated methicillin-resistant S. aureus USA300
A geographic variant of the Staphylococcus aureus Panton-Valentine leukocidin toxin and the origin of community-associated methicillin-resistant S. aureus USA300
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DOI：
10.1086/524684
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发表时间：
2008-01-15
影响因子：
6.4
通讯作者：
Amrine-Madsen, Heather
中科院分区：
文献类型：
--
作者：
O'Hara, F. Patrick;Guex, Nicolas;Amrine-Madsen, Heather
背景在美国，大多数最近社区相关的耐甲氧西林金黄色葡萄球菌（MRSA）感染是由单一克隆USA 300引起的。USA 300分泌Panton-Valentine杀白细胞素（PVL）毒素，其与高毒力感染相关。对174株S.从全球临床样本中分离出金黄色葡萄球菌。我们结合系统发育重建和蛋白质建模的方法来分析PVL的遗传变异。在1726个位点中有12个位点检测到核苷酸变异。两个PVL序列变体，R变体和H变体，根据nt 527处的取代鉴定。在美国获得的序列中，96.7%携带R变体，而在美国以外获得的序列中，95.6%携带H变体; 91.3%的MRSA分离株携带R变体，91.3%的甲氧西林敏感菌株携带H变体。PVL的分子模型显示了氨基酸取代可能影响PVL功能的3种机制。所有采样PVL基因似乎共享一个最近的共同祖先，并通过克隆扩张和水平转移的组合传播。美国分离株携带一种与MRSA感染密切相关的PVL变体。蛋白质建模表明，这种变体可能具有功能意义。我们对USA 300的起源提出了一个假说。
Background. The majority of recent community-associated methicillin-resistant Staphylococcus aureus (MRSA) infections in the United States have been caused by a single clone, USA300. USA300 secretes Panton-Valentine leukocidin (PVL) toxin, which is associated with highly virulent infections.Methods. We sequenced the PVL genes of 174 S. aureus isolates from a global clinical sample. We combined phylogenetic reconstruction and protein modeling methods to analyze genetic variation in PVL.Results. Nucleotide variation was detected at 12 of 1726 sites. Two PVL sequence variants, the R variant and the H variant, were identified on the basis of a substitution at nt 527. Of sequences obtained in the United States, 96.7% harbor the R variant, whereas 95.6% of sequences obtained outside the United States harbor the H variant; 91.3% of MRSA isolates harbor the R variant, and 91.3% of methicillin-susceptible strains harbor the H variant. A molecular model of PVL shows 3 mechanisms by which the amino acid substitution may affect PVL function.Conclusions. All sampled PVL genes appear to share a recent common ancestor and spread via a combination of clonal expansion and horizontal transfer. US isolates harbor a variant of PVL that is strongly associated with MRSA infections. Protein modeling reveals that this variant may have functional significance. We propose a hypothesis for the origin of USA300.