Cytolysin-dependent evasion of lysosomal killing
Cytolysin-dependent evasion of lysosomal killing
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DOI：
10.1073/pnas.0408721102
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发表时间：
2005-04-05
影响因子：
11.1
通讯作者：
Wessels, MR
中科院分区：
文献类型：
--
作者：
Håkansson, A;Bentley, CC;Wessels, MR
局部宿主防御限制了致病菌从粘膜定植部位的增殖和全身传播。对于不能在细胞内生长的链球菌等病原体，上皮细胞的内化和杀伤有助于控制细菌的生长和传播。在这里，我们发现A群链球菌（GAS），链球菌喉咙痛和侵袭性软组织感染的病原体，逃避咽上皮细胞的内化和细胞内杀伤。胆固醇结合细胞毒素溶链素O （SLO）的产生阻止了GAS进入溶酶体的内化。与之形成鲜明对比的是，在SLO生产过程中出现缺陷的GAS被直接内化或迅速转运到溶酶体中，在溶酶体中，它们被ph依赖机制杀死。由于SLO是许多革兰氏阳性细菌产生的胆固醇依赖性细胞溶素的原型，因此细胞溶素介导的逃避溶酶体杀伤可能是保护这些病原体不被宿主上皮细胞清除的一般机制。
Local host defenses limit proliferation and systemic spread of pathogenic bacteria from sites of mucosal colonization. For pathogens such as streptococci that fail to grow intracellularly, internalization and killing by epithelial cells contribute to the control of bacterial growth and dissemination. Here, we show that group A Streptococcus (GAS), the agent of streptococcal sore throat and invasive soft tissue infections, evades internalization and intracellular killing by pharyngeal epithelial cells. Production of the cholesterol-binding cytotoxin streptolysin O (SLO) prevented internalization of GAS into lysosomes. In striking contrast, GAS rendered defective in production of SLO were internalized directly or rapidly transported into lysosomes, where they were killed by a pH-dependent mechanism. Because SLO is the prototype of cholesterol-dependent cytolysins produced by many Gram-positive bacteria, cytolysin-mediated evasion of lysosomal killing may be a general mechanism to protect such pathogens from clearance by host epithelial cells.