Proteomics uncovers extreme heterogeneity in the Staphylococcus aureus exoproteome due to genomic plasticity and variant gene regulation
Proteomics uncovers extreme heterogeneity in the Staphylococcus aureus exoproteome due to genomic plasticity and variant gene regulation
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DOI：
10.1002/pmic.200900313
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发表时间：
2010-04-01
期刊：
影响因子：
3.4
通讯作者：
Engelmann, Susanne
中科院分区：
文献类型：
--
作者：
Ziebandt, Anne-Kathrin;Kusch, Harald;Engelmann, Susanne
对至少13个金黄色葡萄球菌分离株的测序表明，基因组的可塑性对毒力因子的谱系有显著影响。然而，基因组测序并不能揭示个别分离株表达哪些基因。因此，在这里，我们对金黄色葡萄球菌外蛋白质组的组成和变异性进行了全面的调查。这包括多位点序列分型、毒力基因和多重聚合酶链式反应的原噬菌体分析，以及使用2-DE对分泌蛋白的蛋白质组学分析。对25株临床分离株外蛋白质组的分析表明，63株已鉴定的分泌性蛋白中只有7株是由所有分离株产生的，这表明同一种细菌的外蛋白质组具有很高的异质性。最有趣的是，观察到的变异不仅是由于基因组的可塑性，也是由于转录和转录后调控的差异导致分泌蛋白产生了前所未有的差异。我们的数据表明，对毒力基因保守模式的基因组研究需要细胞外蛋白模式的分析来评估像金黄色葡萄球菌这样的细菌病原体的全部毒力潜力。重要的是，金黄色葡萄球菌分泌的毒力因子的广泛变异性也表明，针对这种病原体的保护性疫苗的开发需要精心选择总是产生的抗原的组合。
Sequencing of at least 13 Staphylococcus aureus isolates has shown that genomic plasticity impacts significantly on the repertoire of virulence factors. However, genome sequencing does not reveal which genes are expressed by individual isolates. Here, we have therefore performed a comprehensive survey of the composition and variability of the S. aureus exoproteome. This involved multilocus sequence typing, virulence gene, and prophage profiling by multiplex PCR, and proteomic analyses of secreted proteins using 2-DE. Dissection of the exoproteomes of 25 clinical isolates revealed that only seven out of 63 identified secreted proteins were produced by all isolates, indicating a remarkably high exoproteome heterogeneity within one bacterial species. Most interesting, the observed variations were caused not only by genome plasticity, but also by an unprecedented variation in secretory protein production due to differences in transcriptional and post-transcriptional regulation. Our data imply that genomic studies on virulence gene conservation patterns need to be complemented by analyses of the extracellular protein pattern to assess the full virulence potential of bacterial pathogens like S. aureus. Importantly, the extensive variability of secreted virulence factors in S. aureus also suggests that development of protective vaccines against this pathogen requires a carefully selected combination of invariably produced antigens.