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  PIP5KI gamma 90-generated phosphatidylinositol-4,5-bisphosphate promotes the uptake of Staphylococcus aureus by host cells

Shi, Y., Berking, A., Baade, T., Legate, K. R., Fässler, R., & Hauck, C. R. (2021). PIP5KI gamma 90-generated phosphatidylinositol-4,5-bisphosphate promotes the uptake of Staphylococcus aureus by host cells. Molecular Microbiology, (00), 1-19. doi:10.1111/mmi.14807.

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© 2021 The Authors. Open access funding enabled and organized by Projekt DEAL.
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 Creators:
Shi, Yong1, Author
Berking, Anne1, Author
Baade, Timo1, Author
Legate, Kyle R.2, Author              
Fässler, Reinhard2, Author              
Hauck, Christof R.1, Author
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1external, ou_persistent22              
2Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

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Free keywords: FIBRONECTIN-BINDING PROTEIN; FOCAL ADHESION KINASE; I PHOSPHATIDYLINOSITOL-4-PHOSPHATE 5-KINASES; PHOSPHATE KINASE; INTEGRIN ACTIVATION; BARTONELLA-HENSELAE; STRUCTURAL BASIS; PLASMA-MEMBRANE; PIPKI-GAMMA; TALINBiochemistry & Molecular Biology; Microbiology; fibronectin-binding protein; internalization; phosphatidylinositol-4; 5-bisphosphate; phosphatidylinositol-4-phosphate-5-kinase; Staphylococcus aureus;
 Abstract: 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 gamma (PIP5KI gamma) plays an important role in bacterial internalization. Specific ablation of the talin and FAK-binding motif in PIP5KI gamma 90 reduced bacterial invasion, which could be rescued by reexpression of an active, but not inactive PIP5KI gamma 90. Furthermore, PIP5KI gamma 90-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.

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Language(s): eng - English
 Dates: 2021-09-13
 Publication Status: Published online
 Pages: 19
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000705170200001
DOI: 10.1111/mmi.14807
 Degree: -

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Title: Molecular Microbiology
  Other : Mol. Microbiol.
Source Genre: Journal
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Publ. Info: Oxford : Blackwell Science
Pages: - Volume / Issue: (00) Sequence Number: - Start / End Page: 1 - 19 Identifier: ISSN: 0950-382X
CoNE: https://pure.mpg.de/cone/journals/resource/954925574950