The Listeria monocytogenes hemolysin has an acidic pH optimum to compartmentalize activity and prevent damage to infected host cells.
The Listeria monocytogenes hemolysin has an acidic pH optimum to compartmentalize activity and prevent damage to infected host cells.
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DOI：
10.1083/jcb.200201081
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发表时间：
2002-03-18
期刊：
影响因子：
--
通讯作者：
Portnoy DA
中科院分区：
文献类型：
--
作者：
Glomski IJ;Gedde MM;Tsang AW;Swanson JA;Portnoy DA
单核细胞增生李斯特菌是一种兼性胞内病原菌，它能从吞噬体中逃逸并在宿主细胞胞质中生长。孔形成的胆固醇依赖性溶细胞素，大肠杆菌溶血素O（LLO），介导细菌从囊泡逃逸，并且在酸性pH下比中性pH下活性高10倍。通过交换来自pH不敏感的直向同源物产气荚膜梭菌溶血素O（PFO）的不同残基，我们鉴定了亮氨酸461为致病性李斯特菌特有的，并且负责LLO的酸性pH最佳值。在中性pH下，PFO中亮氨酸461转化为苏氨酸使LLO的溶血活性增加了近10倍。合成LLO L461T的单核细胞增多症（从其在细菌染色体上的内源性位点表达）导致小鼠淋病模型中100倍的毒力缺陷。这些细菌从酸性吞噬体中逃脱，最初在细胞中正常生长并在细胞间扩散，但过早地渗透宿主膜并杀死细胞。这些数据表明，LLO的酸性pH最佳值是由适应性突变引起的，该适应性突变用于限制对酸性囊泡的细胞溶解活性并防止宿主胞质溶胶中的损伤，这也是宿主细胞用于区室化溶酶体水解酶的策略。
Listeria monocytogenes is a facultative intracellular bacterial pathogen that escapes from a phagosome and grows in the host cell cytosol. The pore-forming cholesterol-dependent cytolysin, listeriolysin O (LLO), mediates bacterial escape from vesicles and is ∼10-fold more active at an acidic than neutral pH. By swapping dissimilar residues from a pH-insensitive orthologue, perfringolysin O (PFO), we identified leucine 461 as unique to pathogenic Listeria and responsible for the acidic pH optimum of LLO. Conversion of leucine 461 to the threonine present in PFO increased the hemolytic activity of LLO almost 10-fold at a neutral pH. L. monocytogenes synthesizing LLO L461T, expressed from its endogenous site on the bacterial chromosome, resulted in a 100-fold virulence defect in the mouse listeriosis model. These bacteria escaped from acidic phagosomes and initially grew normally in cells and spread cell to cell, but prematurely permeabilized the host membrane and killed the cell. These data show that the acidic pH optimum of LLO results from an adaptive mutation that acts to limit cytolytic activity to acidic vesicles and prevent damage in the host cytosol, a strategy also used by host cells to compartmentalize lysosomal hydrolases.
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血素素在单核细胞增生李斯特菌的细胞内生长中的作用。
DOI：
10.1084/jem.167.4.1459
发表时间：
1988-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Portnoy DA;Jacks PS;Hinrichs DJ
通讯作者：
Hinrichs DJ
影响因子：
3.6
作者：
Kayal, S;Lilienbaum, A;Berche, P
通讯作者：
Berche, P
影响因子：
3.1
作者：
Moors, MA;Levitt, B;Portnoy, DA
通讯作者：
Portnoy, DA
影响因子：
3.1
作者：
Sibelius, U;Schulz, EC;Grimminger, F
通讯作者：
Grimminger, F
影响因子：
7.8
作者：
Skoble, J;Auerbuch, V;Portnoy, DA
通讯作者：
Portnoy, DA