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PIP5KIγ90‐generated phosphatidylinositol‐4,5‐bisphosphate promotes the uptake of Staphylococcus aureus by host cells
Author(s) -
Shi Yong,
Berking Anne,
Baade Timo,
Legate Kyle R.,
Fässler Reinhard,
Hauck Christof R.
Publication year - 2021
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.14807
Subject(s) - internalization , phosphatidylinositol , phosphatidylinositol 4,5 bisphosphate , biology , microbiology and biotechnology , focal adhesion , kinase , staphylococcus aureus , phosphatase , pi , gene knockdown , integrin , pleckstrin homology domain , biochemistry , signal transduction , phosphorylation , cell , bacteria , gene , genetics
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‐P 2 ), we investigated the roles of PI‐4,5‐P 2 and PI‐4,5‐P 2 ‐producing enzymes in cellular invasion by S. aureus . PI‐4,5‐P 2 accumulated upon contact of S. aureus with the host cell, and targeting of an active PI‐4,5‐P 2 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‐P 2 levels in the plasma membrane but reduced the accumulation of PI‐4,5‐P 2 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‐P 2 by a focal adhesion‐associated lipid kinase for integrin‐mediated internalization of S. aureus .