PIP5KIγ90‐generated phosphatidylinositol‐4,5‐bisphosphate promotes the uptake of Staphylococcus aureus by host cells

Autor: Kyle R. Legate, Reinhard Fässler, Timo Baade, Christof R. Hauck, Yong Shi, Anne Berking
Rok vydání: 2021
Předmět:
Phosphatidylinositol 4
5-Diphosphate
Integrins
Staphylococcus aureus
media_common.quotation_subject
Phosphatase
Biology
Bacterial Physiological Phenomena
medicine.disease_cause
Microbiology
Bacterial Adhesion
chemistry.chemical_compound
Bacterial Proteins
ddc:570
medicine
Humans
Internalization
Molecular Biology
media_common
chemistry.chemical_classification
Gene knockdown
Kinase
Cell Membrane
Staphylococcal Infections
Cell biology
Phosphotransferases (Alcohol Group Acceptor)
HEK293 Cells
Enzyme
chemistry
Phosphatidylinositol 4
5-bisphosphate
Focal Adhesion Protein-Tyrosine Kinases
Host-Pathogen Interactions
fibronectin-binding protein
internalization
phosphatidylinositol-4
5-bisphosphate
30 phosphatidylinositol-4-phosphate-5-kinase
Staphylococcus aureus
Phosphorylation
Protein Binding
Signal Transduction
Zdroj: Molecular Microbiology
ISSN: 1365-2958
0950-382X
DOI: 10.1111/mmi.14807
Popis: 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 re-expression 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 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. published
Databáze: OpenAIRE
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