Genetic Diversity of Staphylocoagulase Genes (coa): Insight into the Evolution of Variable Chromosomal Virulence Factors in Staphylococcus aureus

BackgroundThe production of staphylocoagulase (SC) causing the plasma coagulation is one of the important characteristics of Staphylococcus aureus. Although SCs have been classified into 10 serotypes based on the differences in the antigenicity, genetic bases for their diversities and relatedness to chromosome types are poorly understood.Methodology/Principal FindingsWe compared the nucleotide sequences of 105 SC genes (coa), 59 of which were determined in this study. D1 regions, which contain prothrombin-activating and -binding domains and are presumed to be the binding site of each type-specific antiserum, were classified into twelve clusters having more than 90% nucleotide identities, resulting to create two novel SC types, XI and XII, in addition to extant 10 types. Nine of the twelve SC types were further subdivided into subtypes based on the differences of the D2 or the central regions. The phylogenetical relations of the D1 regions did not correlate exactly with either one of agr types and multilocus sequence types (STs). In addition, genetic analysis showed that recombination events have occurred in and around coa. So far tested, STs of 126 S. aureus strains correspond to the combination of SC type and agr type except for the cases of CC1 and CC8, which contained two and three different SC types, respectively.ConclusionThe data suggested that the evolution of coa was not monophyletic in the species. Chromosomal recombination had occurred at coa and agr loci, resulting in the carriage of the combinations of allotypically different important virulence determinants in staphylococcal chromosome.背景：导致血浆凝固的葡萄球菌凝固酶（Staphylocoagulase, SC）的产生，是金黄色葡萄球菌（Staphylococcus aureus）的重要特征之一。尽管基于抗原性差异，SC已被划分为10个血清型，但学界对其多样性的遗传基础以及其与染色体型的关联仍知之甚少。 方法与结果：本研究比对了105条SC编码基因（coa）的核苷酸序列，其中59条为本研究首次测定。包含凝血酶原激活域与结合域、且被认为是各型特异性抗血清结合位点的D1区域，被划分为12个核苷酸同源性≥90%的聚类；这一划分在已有的10个血清型之外，新增了XI和XII两个全新的SC型别。12个SC型别中的9个，还可根据D2区域或核心区域的差异进一步划分为亚型。D1区域的系统发育关系，与agr型别以及多位点序列分型（Multilocus Sequence Types, STs）均未呈现严格的关联。此外，遗传分析显示，coa基因内部及其侧翼区域均发生过重组事件。截至目前的检测结果显示，126株金黄色葡萄球菌的STs分型结果与SC型别和agr型别的组合一一对应，但克隆复合体1（CC1）与克隆复合体8（CC8）除外：前者包含2种不同的SC型别，后者则包含3种。 结论：本研究数据表明，在金黄色葡萄球菌这一物种中，coa基因的演化并非单系起源。染色体上的coa与agr基因座均发生过重组事件，这使得葡萄球菌染色体上得以携带异型的重要毒力决定因子组合。