Sabat Artur J, Wladyka Benedykt, Kosowska-Shick Klaudia, Grundmann Hajo, van Dijl Jan Maarten, Kowal Julia, Appelbaum Peter C, Dubin Adam, Hryniewicz Waleria
National Medicines Institute, 00-725 Warsaw, Poland.
BMC Microbiol. 2008 Jul 29;8:129. doi: 10.1186/1471-2180-8-129.
Staphylococcus aureus expresses several proteases, which are thought to contribute to the virulence of this bacterium. Here we focus on aureolysin, the major thermolysin-like metalloprotease. Despite the importance of aureolysin in the physiology and pathogenesis of S. aureus, relatively little information was so far available concerning the aur gene diversity and mobility within and between the major subdivisions of the S. aureus population. Therefore, an epidemiologically and genetically diverse collection of S. aureus strains was used to determine the range of aureolysin (aur) gene polymorphism.
Sequence analyses support the conclusion that the aur gene occurs in two distinct types of related sequences. The aur gene was much more polymorphic but, at the same time, showed higher purifying selection than genes utilized for multilocus sequence typing (MLST). Gene trees constructed from aur and concatenated MLST genes revealed several putative assortative recombination events (i.e. entire aur gene exchanges) between divergent lineages of S. aureus. Evidence for intragenic recombination events (i.e. exchanges of internal aur segments) across aur genes was also found. The biochemical properties and substrate specificity of the two types of aureolysin purified to homogeneity were studied, revealing minor differences in their affinity to low molecular weight synthetic substrates.
Although numerous nucleotide differences were identified between the aur alleles studied, our findings showed that a strong purifying selection is acting on the aur gene. Moreover, our study distinguishes between homologous exchanges of the entire aur gene (assortative recombination) between divergent S. aureus lineages and recombination events within aur genes.
金黄色葡萄球菌表达多种蛋白酶，这些蛋白酶被认为有助于该细菌的毒力。在此，我们聚焦于金黄色葡萄球菌主要的嗜热菌蛋白酶样金属蛋白酶——奥罗溶素。尽管奥罗溶素在金黄色葡萄球菌的生理学和发病机制中具有重要性，但迄今为止，关于奥罗溶素（aur）基因在金黄色葡萄球菌群体主要亚群内部及其之间的多样性和移动性的信息相对较少。因此，我们使用了一组在流行病学和遗传学上具有多样性的金黄色葡萄球菌菌株来确定奥罗溶素（aur）基因多态性的范围。
序列分析支持以下结论：aur基因存在于两种不同类型的相关序列中。aur基因具有更高的多态性，但与此同时，与用于多位点序列分型（MLST）的基因相比，其纯化选择程度更高。由aur基因和串联的MLST基因构建的基因树揭示了金黄色葡萄球菌不同谱系之间存在几个假定的选择性重组事件（即整个aur基因交换）。还发现了跨aur基因的基因内重组事件（即aur内部片段交换）的证据。我们研究了纯化至均一的两种类型奥罗溶素的生化特性和底物特异性，结果显示它们对低分子量合成底物的亲和力存在细微差异。
尽管在所研究的aur等位基因之间鉴定出了许多核苷酸差异，但我们的研究结果表明，一种强大的纯化选择作用于aur基因。此外，我们的研究区分了金黄色葡萄球菌不同谱系之间整个aur基因的同源交换（选择性重组）和aur基因内的重组事件。
