ArticleMolecular biology of the cell2005
The phosphoinositol-3-kinase-protein kinase B/Akt pathway is critical for Pseudomonas aeruginosa strain PAK internalization.
Article in Molecular biology of the cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 129 citations in OpenAlex.
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- IntratumoralAnimals : an open access journal from MDPI · 2026Article
- Comparison of virulence factors genes between exoU and exoS Pseudomonas aeruginosa in microbial keratitis.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Article
- PTEN modulates urinary tract infection susceptibility and shapes urothelial antibacterial defenses.Life science alliance · 2025Article
- Therapeutic targeting of ocular diseases with emphasis on PI3K/Akt, and OPRL pathways by Hedera helix L. saponins: a new approach for the treatment of Pseudomonas aeruginosa-induced bacterial keratitis.Natural products and bioprospecting · 2025Article
- The Role of PI3k-Gamma Modulation in Bacterial Infection: A Review of the Literature and Selected Experimental Observations.Antibiotics (Basel, Switzerland) · 2025Review
- In silico molecular targets, docking, dynamics simulation and physiologically based pharmacokinetics modeling of oritavancin.BMC pharmacology & toxicology · 2024Article
- Pseudomonas aeruginosa breaches respiratory epithelia through goblet cell invasion in a microtissue model.Nature microbiology · 2024Article
- Inverted apicobasal polarity in health and disease.Journal of cell science · 2024Review
- Baicalin Attenuates Panton-Valentine Leukocidin (PVL)-Induced Cytoskeleton Rearrangement via Regulating the RhoA/ROCK/LIMK and PI3K/AKT/GSK-3β Pathways in Bovine Mammary Epithelial Cells.International journal of molecular sciences · 2023Article
- Structural insights into PA3488-mediated inactivation of Pseudomonas aeruginosa PldA.Nature communications · 2022Article
- Article
- Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics.Signal transduction and targeted therapy · 2022Review
- Non-Canonical Host Intracellular Niche Links to New Antimicrobial Resistance Mechanism.Pathogens (Basel, Switzerland) · 2022Review
- Molecular Mechanisms Involved in Pseudomonas aeruginosa Bacteremia.Advances in experimental medicine and biology · 2022Review
- Article
- The Gb3-enriched CD59/flotillin plasma membrane domain regulates host cell invasion by Pseudomonas aeruginosa.Cellular and molecular life sciences : CMLS · 2021Article
- Transcriptional Studies onFrontiers in cellular and infection microbiology · 2021Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Several Pseudomonas aeruginosa strains are internalized by epithelial cells in vitro and in vivo, but the host pathways usurped by the bacteria to enter nonphagocytic cells are not clearly understood. Here, we report that internalization of strain PAK into epithelial cells triggers and requires activation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B/Akt (Akt). Incubation of Madin-Darby canine kidney (MDCK) or HeLa cells with the PI3K inhibitors LY294002 (LY) or wortmannin abrogated PAK uptake. Addition of the PI3K product phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] to polarized MDCK cells was sufficient to increase PAK internalization. PtdIns(3,4,5)P3 accumulated at the site of bacterial binding in an LY-dependent manner. Akt phosphorylation correlated with PAK invasion. The specific Akt phosphorylation inhibitor SH-5 inhibited PAK uptake; internalization also was inhibited by small interfering RNA-mediated depletion of Akt phosphorylation. Expression of constitutively active Akt was sufficient to restore invasion when PI3K signaling was inhibited. Together, these results demonstrate that the PI3K signaling pathway is necessary and sufficient for the P. aeruginosa entry and provide the first example of a bacterium that requires Akt for uptake into epithelial cells.
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