Unique virulence role of post-translocational chaperone PrsA in shaping Streptococcus pyogenes secretome.
Unique virulence role of post-translocational chaperone PrsA in shaping Streptococcus pyogenes secretome.
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DOI：
10.1080/21505594.2021.1982501
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发表时间：
2021-12
期刊：
影响因子：
5.2
通讯作者：
Chang YC
中科院分区：
文献类型：
--
作者：
Wu ZY;Campeau A;Liu CH;Gonzalez DJ;Yamaguchi M;Kawabata S;Lu CH;Lai CY;Chiu HC;Chang YC
化脓性链球菌（Streptococcus pyogenes，GAS）是一种严重危害人类健康的病原菌，可引起多种疾病和自身免疫性疾病。GAS感染的发病机制主要依赖于细胞壁相关和分泌的毒力蛋白，如粘附素，毒素和外切酶的广泛网络的产生。PrsA是革兰氏阳性菌中普遍表达的唯一的细胞外小蛋白型肽基脯氨酰异构酶，已被认为有助于新出口蛋白质的折叠和成熟以获得其天然构象和活性。两个PrsA蛋白，PrsA1和PrsA2，已被确定在GAS，但各自的贡献GAS发病机制仍然在很大程度上未知。通过结合比较蛋白质组学和表型分析方法，我们证明了PrsA亚型都需要以独特和重叠的方式维持GAS蛋白质组稳态和毒性相关性状。在小鼠软组织感染模型中，两种PrsA在GAS中的失活引起生物膜形成、宿主粘附、感染诱导的细胞毒性和体内毒力的显著损害。蛋白质组学和表型数据的一致性清楚地表明了PrsA在GAS全毒力中的重要作用。
Streptococcus pyogenes (group A Streptococcus, GAS) is a strict human pathogen causing a broad spectrum of diseases and a variety of autoimmune sequelae. The pathogenesis of GAS infection mostly relies on the production of an extensive network of cell wall-associated and secreted virulence proteins, such as adhesins, toxins, and exoenzymes. PrsA, the only extracellular parvulin-type peptidyl-prolyl isomerase expressed ubiquitously in Gram-positive bacteria, has been suggested to assist the folding and maturation of newly exported proteins to acquire their native conformation and activity. Two PrsA proteins, PrsA1 and PrsA2, have been identified in GAS, but the respective contribution of each PrsA in GAS pathogenesis remains largely unknown. By combining comparative proteomic and phenotypic analysis approaches, we demonstrate that both PrsA isoforms are required to maintain GAS proteome homeostasis and virulence-associated traits in a unique and overlapping manner. The inactivation of both PrsA in GAS caused remarkable impairment in biofilm formation, host adherence, infection-induced cytotoxicity, and in vivo virulence in a murine soft tissue infection model. The concordance of proteomic and phenotypic data clearly features the essential role of PrsA in GAS full virulence.
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DOI：
10.1074/jbc.m114.602847
发表时间：
2014-11-14
期刊：
The Journal of biological chemistry
影响因子：
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