Streptolysin S Contributes to Group A Streptococcal Translocation across an Epithelial Barrier
Streptolysin S Contributes to Group A Streptococcal Translocation across an Epithelial Barrier
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DOI：
10.1074/jbc.m110.171504
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发表时间：
2011-01-28
影响因子：
4.8
通讯作者：
Kawabata, Shigetada
中科院分区：
文献类型：
--
作者：
Sumitomo, Tomoko;Nakata, Masanobu;Kawabata, Shigetada
A群化脓性链球菌（GAS）是一种引起局部化脓性感染和严重侵袭性疾病的人类病原体。气体的全身传播是由细菌穿透咽上皮屏障或受损皮肤引起的。为了深入了解GAS穿透上皮屏障的机制，我们试图确定参与该过程的细菌和宿主因素。从侵袭性发作中恢复的临床GAS分离物的转座子突变文库的筛选允许鉴定链溶素S （SLS）作为促进GAS易位的新因素。值得注意的是，野生型菌株有效地在上皮单层上易位，伴随着跨上皮电阻的降低和跨膜连接蛋白（包括occludin和E-cadherin）的切割。与野生型菌株相比，被编码SLS的sagA基因缺失突变体感染后，细胞间连接完整性的丧失受到抑制。有趣的是，在GAS感染后，钙蛋白酶与e -钙粘蛋白一起被募集到质膜上。此外，细菌的易位和连接的不稳定被药理学钙蛋白酶抑制剂或遗传干扰钙蛋白酶部分抑制。我们的数据表明SLS的潜在功能，通过与宿主半胱氨酸蛋白酶calpain协同降解上皮细胞间连接，促进GAS侵入更深的组织。
Group A Streptococcus pyogenes (GAS) is a human pathogen that causes local suppurative infections and severe invasive diseases. Systemic dissemination of GAS is initiated by bacterial penetration of the epithelial barrier of the pharynx or damaged skin. To gain insight into the mechanism by which GAS penetrates the epithelial barrier, we sought to identify both bacterial and host factors involved in the process. Screening of a transposon mutant library of a clinical GAS isolate recovered from an invasive episode allowed identification of streptolysin S (SLS) as a novel factor that facilitates the translocation of GAS. Of note, the wild type strain efficiently translocated across the epithelial monolayer, accompanied by a decrease in transepithelial electrical resistance and cleavage of transmembrane junctional proteins, including occludin and E-cadherin. Loss of integrity of intercellular junctions was inhibited after infection with a deletion mutant of the sagA gene encoding SLS, as compared with those infected with the wild type strain. Interestingly, following GAS infection, calpain was recruited to the plasma membrane along with E-cadherin. Moreover, bacterial translocation and destabilization of the junctions were partially inhibited by a pharmacological calpain inhibitor or genetic interference with calpain. Our data indicate a potential function of SLS that facilitates GAS invasion into deeper tissues via degradation of epithelial intercellular junctions in concert with the host cysteine protease calpain.