M1 protein triggers a phosphoinositide cascade for group A Streptococcus invasion of epithelial cells.
M1 protein triggers a phosphoinositide cascade for group A Streptococcus invasion of epithelial cells.
复制标题
M1 蛋白触发 A 组链球菌入侵上皮细胞的磷酸肌醇级联反应。
DOI：
10.1128/iai.71.10.5823-5830.2003
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发表时间：
2003
影响因子：
3.1
通讯作者：
Cleary,PPatrick
中科院分区：
文献类型：
--
作者：
Purushothaman,SaiSudha;Wang,Beinan;Cleary,PPatrick
细菌对非吞噬细胞的入侵为宿主防御和抗生素的持续和逃避提供了有利的生态位。M蛋白是一种主要的毒力因子，因为它促进了AStreatment组（GAS）对上皮细胞的高频率侵袭，并且还使细菌对吞噬作用具有抗性。在这项研究中，我们研究了来自血清型M1菌株90-226的M1蛋白在调节哺乳动物细胞信号转导和细胞骨架重排中的作用。磷脂酰肌醇3-激酶（PI 3-K）抑制剂LY 294002和渥曼青霉素分别抑制GAS对上皮细胞的侵袭，抑制率分别为75%和80%，但不能抑制沙门氏菌的侵袭。此外，上皮细胞瞬时转染显性负性p85和p110基因，PI 3-K的调节和催化亚基，分别是能够被GAS入侵。为了分离其他链球菌毒力因子对M蛋白的影响，我们将M1蛋白表达于乳酸乳球菌表面。乳酸杆菌（pLM 1）在体外有效地侵入上皮细胞，PI 3-K抑制剂阻断了90%的这种侵入。纯化的可溶性M1蛋白刺激上皮细胞上的应力纤维和肌动蛋白凝灰岩的形成。LY 294002和wortmannin抑制这些细胞变化。磷酸肌醇类似物也抑制GAS对上皮细胞的侵袭。因此，M1蛋白直接或通过结合的纤连蛋白启动依赖于脂质激酶PI 3-K途径的信号，这为内化细菌的细胞骨架重排铺平了道路。
Invasion of nonphagocytic cells by bacteria provides a favorable niche for persistence and evasion of host defenses and antibiotics. M protein is a major virulence factor because it promotes high-frequency invasion of epithelial cells by group AStreptococcus(GAS) and also renders the bacterium resistant to phagocytosis. In this study, we investigated the role of M1 protein from serotype M1 strain 90-226 in regulating mammalian signal transduction and cytoskeletal rearrangement for bacterial entry. LY294002 and wortmannin, which are inhibitors of phosphatidylinositol 3-kinase (PI 3-K) blocked invasion of epithelial cells by GAS by 75 and 80%, respectively, but failed to inhibit invasion bySalmonella entericaserovar Typhimurium. Also, epithelial cells transiently transfected with dominant negative p85 and p110 genes, the regulatory and catalytic subunits of PI 3-K, respectively, were less able to be invaded by GAS. To separate the influence of other streptococcal virulence factors from M protein,Lactococcus lactiswas engineered to express M1 protein on its surface.L. lactis(pLM1) invaded epithelial cells efficiently in vitro, and PI 3-K inhibitors blocked 90% of this invasion. Purified soluble M1 protein stimulated the formation of stress fibers and actin tuffs on epithelial cells. LY294002 and wortmannin inhibited these cellular changes. A phosphoinositide analogue also inhibited the invasion of epithelial cells by GAS. Therefore, M1 protein, either directly or via bound fibronectin, initiates signals that depend on the lipid kinase PI 3-K pathway, which paves the way for cytoskeletal rearrangement that internalize the bacterium.