Institute for Biology-Microbiology, Freie Universität Berlin, D-14195 Berlin, Germany; Center for Biotechnology, Bielefeld University, D-33594 Bielefeld, Germany.
Institute for Biology-Microbiology, Freie Universität Berlin, D-14195 Berlin, Germany.
Mol Cell Proteomics. 2018 Dec;17(12):2412-2433. doi: 10.1074/mcp.RA118.001036. Epub 2018 Sep 10.
The spread of methicillin-resistant (MRSA) in the community, hospitals and in livestock is mediated by highly diverse virulence factors that include secreted toxins, superantigens, enzymes and surface-associated adhesins allowing host adaptation and colonization. Here, we combined proteogenomics, secretome and phenotype analyses to compare the secreted virulence factors in selected isolates of the dominant human- and livestock-associated genetic lineages CC8, CC22, and CC398. The proteogenomic comparison revealed 2181 core genes and 1306 accessory genes in 18 isolates reflecting the high genome diversity. Using secretome analysis, we identified 869 secreted proteins with 538 commons in eight isolates of CC8, CC22, and CC398. These include 64 predicted extracellular and 37 cell surface proteins that account for 82.4% of total secretome abundance. Among the top 10 most abundantly secreted virulence factors are the major autolysins (Atl, IsaA, Sle1, SAUPAN006375000), lipases and lipoteichoic acid hydrolases (Lip, Geh, LtaS), cytolytic toxins (Hla, Hlb, PSMβ1) and proteases (SspB). The CC398 isolates showed lower secretion of cell wall proteins, but higher secretion of α- and β-hemolysins (Hla, Hlb) which correlated with an increased Agr activity and strong hemolysis. CC398 strains were further characterized by lower biofilm formation and staphyloxanthin levels because of decreased SigB activity. Overall, comparative secretome analyses revealed CC8- or CC22-specific enterotoxin and Spl protease secretion as well as Agr- and SigB-controlled differences in exotoxin and surface protein secretion between human-specific and zoonotic lineages of .
耐甲氧西林金黄色葡萄球菌（MRSA）在社区、医院和牲畜中的传播是由高度多样化的毒力因子介导的，这些因子包括分泌毒素、超抗原、酶和表面相关黏附素，使宿主适应和定植。在这里，我们结合蛋白质基因组学、分泌组学和表型分析，比较了选定的人源和动物源遗传谱系 CC8、CC22 和 CC398 中优势分离株的分泌毒力因子。蛋白质基因组学比较显示，18 个分离株中有 2181 个核心基因和 1306 个辅助基因，反映了基因组的高度多样性。通过分泌组分析，我们在 CC8、CC22 和 CC398 的 8 个分离株中鉴定出了 869 种分泌蛋白，其中 538 种在 8 个分离株中共有。这些蛋白包括 64 种预测的细胞外蛋白和 37 种细胞表面蛋白，占总分泌组丰度的 82.4%。在排名前 10 的最丰富分泌毒力因子中，主要自溶酶（Atl、IsaA、Sle1、SAUPAN006375000）、脂肪酶和脂磷壁酸水解酶（Lip、Geh、LtaS）、细胞溶解毒素（Hla、Hlb、PSMβ1）和蛋白酶（SspB）。CC398 分离株的细胞壁蛋白分泌较低，但α-和β-溶血素（Hla、Hlb）分泌较高，这与 Agr 活性增加和强烈溶血有关。CC398 菌株的生物膜形成和粪卟啉水平较低，因为 SigB 活性降低。总的来说，比较分泌组分析显示，CC8 或 CC22 特异性肠毒素和 Spl 蛋白酶分泌，以及 Agr 和 SigB 控制的人源和动物源谱系之间外毒素和表面蛋白分泌的差异。
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