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PIP5KIγ90-generated phosphatidylinositol-4,5-bisphosphate promotes the uptake of Staphylococcus aureus by host cells
Molecular Microbiology ( IF 3.6 ) Pub Date : 2021-09-13 , DOI: 10.1111/mmi.14807
Yong Shi 1 , Anne Berking 1 , Timo Baade 1, 2 , Kyle R Legate 3 , Reinhard Fässler 3 , Christof R Hauck 1, 2
Affiliation  

Staphylococcus aureus, a Gram-positive pathogen, invades cells mainly in an integrin-dependent manner. As the activity or conformation of several integrin-associated proteins can be regulated by phosphatidylinositol-4,5-bisphosphate (PI-4,5-P2), we investigated the roles of PI-4,5-P2 and PI-4,5-P2-producing enzymes in cellular invasion by S. aureus. PI-4,5-P2 accumulated upon contact of S. aureus with the host cell, and targeting of an active PI-4,5-P2 phosphatase to the plasma membrane reduced bacterial invasion. Knockdown of individual phosphatidylinositol-4-phosphate 5-kinases revealed that phosphatidylinositol-4-phosphate 5-kinase γ (PIP5KIγ) plays an important role in bacterial internalization. Specific ablation of the talin and FAK-binding motif in PIP5KIγ90 reduced bacterial invasion, which could be rescued by reexpression of an active, but not inactive PIP5KIγ90. Furthermore, PIP5KIγ90-deficient cells showed normal basal PI-4,5-P2 levels in the plasma membrane but reduced the accumulation of PI-4,5-P2 and talin at sites of S. aureus attachment and overall lower levels of FAK phosphorylation. These results highlight the importance of local synthesis of PI-4,5-P2 by a focal adhesion-associated lipid kinase for integrin-mediated internalization of S. aureus.

中文翻译:

PIP5KIγ90产生的4,5-二磷酸磷脂酰肌醇促进宿主细胞对金黄色葡萄球菌的摄取

金黄色葡萄球菌是一种革兰氏阳性病原体,主要以整合素依赖性方式侵入细胞。由于几种整合素相关蛋白的活性或构象可由 phosphatidylinositol-4,5-bisphosphate (PI-4,5-P 2 ) 调节,我们研究了 PI-4,5-P 2和 PI-4的作用金黄色葡萄球菌侵入细胞时产生,5-P 2的酶。PI-4,5-P 2在金黄色葡萄球菌与宿主细胞接触并靶向活性 PI-4,5- P 2时积累质膜的磷酸酶减少了细菌的侵袭。敲除单个 4-磷酸磷脂酰肌醇 5-激酶表明,4-磷酸磷脂酰肌醇 5-激酶 γ (PIP5KIγ) 在细菌内化中起重要作用。PIP5KIγ90 中 talin 和 FAK 结合基序的特异性消融减少了细菌入侵,这可以通过重新表达活性而非非活性 PIP5KIγ90 来挽救。此外,PIP5KIγ90 缺陷细胞在质膜中显示正常的基础 PI-4,5-P 2水平,但减少了 PI-4,5-P 2和 talin 在金黄色葡萄球菌附着位点的积累和总体较低水平的 FAK磷酸化。这些结果突出了局部合成 PI-4,5-P 2的重要性通过与粘着斑相关的脂质激酶进行整合素介导的金黄色葡萄球菌内化。
更新日期:2021-11-17
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