Identification of Conserved and Species-Specific Functions of the Listeria monocytogenes PrsA2 Secretion Chaperone
Identification of Conserved and Species-Specific Functions of the Listeria monocytogenes PrsA2 Secretion Chaperone
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DOI：
10.1128/iai.00504-15
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发表时间：
2015-10-01
影响因子：
3.1
通讯作者：
Freitag, Nancy E.
中科院分区：
文献类型：
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作者：
Cahoon, Laty A.;Freitag, Nancy E.
革兰氏阳性菌单核细胞增生性李斯特菌是一种兼性细胞内病原体，它依赖于各种蛋白质的调节分泌和活性，这些蛋白质在不同的环境中维持生命。PrsA2是一种分泌型多肽-脯氨酰顺/反式异构酶和伴侣，对肉汤培养中的细菌生长是必需的，但对单核细胞增多性李斯特氏菌的毒力是必不可少的。在宿主感染后，PrsA2有助于分泌蛋白质的适当折叠和活性，这些蛋白质是细菌在宿主胞浆内复制和细菌传播到邻近细胞所必需的。PrsA2是革兰氏阳性分泌伴侣蛋白家族的成员之一，似乎在细菌生理学中发挥重要作用；然而，这些蛋白如何识别它们的底物蛋白或它们的功能在不同的革兰氏阳性物种中保守的程度尚不清楚。因此，我们研究了各种革兰氏阳性菌编码的PRSA蛋白对缺乏prsA2的单核细胞增多性乳杆菌突变体的功能互补作用。对枯草杆菌、化脓性链球菌、肺炎链球菌、变形链球菌、金黄色葡萄球菌和乳酸乳球菌编码的PRSA同源物进行了检测，以寻找与单核细胞增多性乳杆菌致病机制和细菌细胞生理相关的各种表型的功能互补性。我们的结果表明，虽然PrsA2功能的某些方面在不同的革兰氏阳性细菌中广泛保守，但PrsA2对致病所需的单核细胞增多性乳杆菌靶蛋白表现出独特的特异性。因此，单核细胞增生性李斯特菌PrsA2伴侣蛋白在进化上似乎对宿主细胞胞浆内的毒力因子分泌进行了优化，同时仍然保持了与革兰氏阳性蛋白易位的更一般特征相关的活性。
The Gram-positive bacterium Listeria monocytogenes is a facultative intracellular pathogen that relies on the regulated secretion and activity of a variety of proteins that sustain life within diverse environments. PrsA2 has recently been identified as a secreted peptidyl-prolyl cis/trans isomerase and chaperone that is dispensable for bacterial growth in broth culture but essential for L. monocytogenes virulence. Following host infection, PrsA2 contributes to the proper folding and activity of secreted proteins that are required for bacterial replication within the host cytosol and for bacterial spread to adjacent cells. PrsA2 is one member of a family of Gram-positive secretion chaperones that appear to play important roles in bacterial physiology; however, it is not known how these proteins recognize their substrate proteins or the degree to which their function is conserved across diverse Gram-positive species. We therefore examined PrsA proteins encoded by a variety of Gram-positive bacteria for functional complementation of L. monocytogenes mutants lacking prsA2. PrsA homologues encoded by Bacillus subtilis, Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus mutans, Staphylococcus aureus, and Lactococcus lactis were examined for functional complementation of a variety of L. monocytogenes PrsA2-associated phenotypes central to L. monocytogenes pathogenesis and bacterial cell physiology. Our results indicate that while selected aspects of PrsA2 function are broadly conserved among diverse Gram-positive bacteria, PrsA2 exhibits unique specificity for L. monocytogenes target proteins required for pathogenesis. The L. monocytogenes PrsA2 chaperone thus appears evolutionarily optimized for virulence factor secretion within the host cell cytosol while still maintaining aspects of activity relevant to more general features of Gram-positive protein translocation.