The Posttranslocation Chaperone PrsA2 Contributes to Multiple Facets of Listeria monocytogenes Pathogenesis
The Posttranslocation Chaperone PrsA2 Contributes to Multiple Facets of Listeria monocytogenes Pathogenesis
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DOI：
10.1128/iai.00280-09
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发表时间：
2009-07-01
影响因子：
3.1
通讯作者：
Freitag, Nancy E.
中科院分区：
文献类型：
--
作者：
Alonzo, Francis, III;Port, Gary C.;Freitag, Nancy E.
单核细胞增生李斯特菌是一种细胞内致病菌，其毒力依赖于许多分泌的细菌因子的调节表达。与其它革兰氏阳性菌一样，L.单核细胞增多症以未折叠状态穿过细菌膜转移到存在于膜和细胞壁之间的区室。该隔室由于其高密度的负电荷，高浓度的阳离子和低pH值，为蛋白质折叠提出了一个具有挑战性的环境。单核细胞增生毒力PrsA 2是基于含有突变激活形式的prfA（L.单核细胞增生毒力基因表达。prsA 2基因产物是由L.单核细胞增多症;这些蛋白质作为易位后蛋白质伴侣和/或折叠酶起作用。在这项研究中，我们证明了PrsA 2在L.通过促进至少两种关键分泌毒力因子的活性和稳定性，单核细胞增多症的发病机制：嗜酸乳杆菌溶血素O（LLO）和广泛特异性磷脂酶。PrsA 2活性的丧失严重减弱了小鼠的毒力，并损害了宿主细胞中细菌细胞间的传播。相比之下，缺乏prsA 1的突变体类似于野生型细菌的细胞内生长和细胞间传播以及在小鼠中的毒力。因此，PrsA 2与PrsA 1的不同之处在于其对L的稳定性和完全活性的独特要求。单核细胞生成素--一种促进宿主感染的分泌因子。
Listeria monocytogenes is an intracellular bacterial pathogen whose virulence depends on the regulated expression of numerous secreted bacterial factors. As for other gram-positive bacteria, many proteins secreted by L. monocytogenes are translocated across the bacterial membrane in an unfolded state to the compartment existing between the membrane and the cell wall. This compartment presents a challenging environment for protein folding due to its high density of negative charge, high concentrations of cations, and low pH. We recently identified PrsA2 as a gene product required for L. monocytogenes virulence. PrsA2 was identified based on its increased secretion by strains containing a mutationally activated form of prfA, the key regulator of L. monocytogenes virulence gene expression. The prsA2 gene product is one of at least two predicted peptidyl-prolyl cis/trans-isomerases encoded by L. monocytogenes; these proteins function as posttranslocation protein chaperones and/or foldases. In this study, we demonstrate that PrsA2 plays a unique and important role in L. monocytogenes pathogenesis by promoting the activity and stability of at least two critical secreted virulence factors: listeriolysin O (LLO) and a broad-specificity phospholipase. Loss of PrsA2 activity severely attenuated virulence in mice and impaired bacterial cell-to-cell spread in host cells. In contrast, mutants lacking prsA1 resembled wild-type bacteria with respect to intracellular growth and cell-to-cell spread as well as virulence in mice. PrsA2 is thus distinct from PrsA1 in its unique requirement for the stability and full activity of L. monocytogenes-secreted factors that contribute to host infection.