Comparative Secretome Analyses of Human and Zoonotic Staphylococcus aureus Isolates CC8, CC22, and CC398.
Comparative Secretome Analyses of Human and Zoonotic Staphylococcus aureus Isolates CC8, CC22, and CC398.
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DOI：
10.1074/mcp.ra118.001036
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发表时间：
2018-12
期刊：
影响因子：
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通讯作者：
Antelmann H
中科院分区：
文献类型：
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作者：
Busche T;Hillion M;Van Loi V;Berg D;Walther B;Semmler T;Strommenger B;Witte W;Cuny C;Mellmann A;Holmes MA;Kalinowski J;Adrian L;Bernhardt J;Antelmann H
比较了人类和人畜共患金黄色葡萄球菌优势谱系CC8、CC22和CC398的蛋白质基因组和分泌组，揭示了869种蛋白质分泌的基因组和调控差异。在核心分泌组中，101个分泌的或细胞表面固定的毒力因子占总分泌组丰度的82.4%。与人类特异性CC8和CC22相比，CC398菌株表现出较高的α-和ß-溶血素分泌和较低的表面蛋白分泌，导致较强的溶血和较少的生物膜形成。人类和人畜共患金黄色葡萄球菌谱系的蛋白质基因组学和分泌组学比较。从8株金黄色葡萄球菌CC8、CC22和CC398中鉴定出869种分泌蛋白。CC398表面蛋白分泌减少，溶血素和外泌酶分泌增多。分泌体的调节差异可能与CC398中SigB活性降低有关。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素介导的，这些毒力因素包括分泌的毒素、超抗原、酶和允许宿主适应和定植的表面相关粘附素。在这里，我们结合了蛋白质基因组学、分泌组学和表型分析，比较了选定的金黄色葡萄球菌分离物中与人类和牲畜相关的显性遗传谱系CC8、CC22和CC398的分泌毒力因子。蛋白质基因组学比较显示，18株金黄色葡萄球菌的核心基因为2181个，辅助基因为1306个，具有较高的基因组多样性。通过分泌组分析，我们在8株CC8、CC22和CC398中鉴定出869种分泌蛋白，其中538种共有。其中包括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%。前10位最丰富分泌的毒力因子是主要的自溶酶（Atl、IsaA、Sle1、SAUPAN006375000）、脂肪酶和脂质胆酸水解酶（Lip、Geh、LtaS）、细胞溶解毒素（Hla、Hlb、PSMβ1）和蛋白酶（SspB）。CC398分离株细胞壁蛋白分泌较低，α-和β-溶血素（Hla, Hlb）分泌较高，这与Agr活性升高和溶血作用强有关。由于SigB活性降低，CC398菌株的生物膜形成和葡萄黄质水平进一步降低。总体而言，比较分泌组学分析揭示了金黄色葡萄球菌人类特异性和人畜共患谱系之间CC8-或cc22特异性肠毒素和Spl蛋白酶分泌以及Agr和sigb控制的外毒素和表面蛋白分泌的差异。
The proteogenomes and secretomes of dominant human and zoonotic S. aureus lineages CC8, CC22 and CC398 were compared revealing genomic and regulatory differences in the secretion of 869 proteins. In the core secretome, 101 secreted or cell surface anchored virulence factors contribute with 82.4% to total secretome abundance. CC398 isolates showed higher secretion of α- and ß-hemolysins and lower secretion of surface proteins resulting in strong hemolysis and decreased biofilm formation because of lower SigB activity compared to human-specific CC8 and CC22. Highlights Proteogenomics and secretome comparison of human and zoonotic Staphylococcus aureus lineages. 869 secreted proteins identified in eight S. aureus isolates of CC8, CC22 and CC398. CC398 lower secretion of surface proteins and higher secretion of hemolysins and exoenzymes. Regulatory differences in the secretomes could be linked to lower SigB activity in CC398. The spread of methicillin-resistant Staphylococcus aureus (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 S. aureus 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 S. aureus 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 S. aureus.