ArticleThe Journal of biological chemistry2009
Cdc42 and the phosphatidylinositol 3-kinase-Akt pathway are essential for PspC-mediated internalization of pneumococci by respiratory epithelial cells.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- Negative Cross-Talk between TLR2/4-Independent AMPKα1 and TLR2/4-Dependent JNK RegulatesJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- Role of Host Small GTPases in Apicomplexan Parasite Infection.Microorganisms · 2022Review
- Quantitative trait loci and transcriptome signatures associated with avian heritable resistance to Campylobacter.Scientific reports · 2021Article
- Streptococcus pneumoniae hijacks host autophagy by deploying CbpC as a decoy for Atg14 depletion.EMBO reports · 2020Article
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- Microbial uptake by the respiratory epithelium: outcomes for host and pathogen.FEMS microbiology reviews · 2019Review
- Human Bronchial Epithelial Cells Inhibit Aspergillus fumigatus Germination of Extracellular Conidia via FleA Recognition.Scientific reports · 2018Article
- Chronic Cigarette Smoke Mediated Global Changes in Lung Mucoepidermoid Cells: A Phosphoproteomic Analysis.Omics : a journal of integrative biology · 2017Article
- Induction of Central Host Signaling Kinases during Pneumococcal Infection of Human THP-1 Cells.Frontiers in cellular and infection microbiology · 2016Article
- Pneumococcal Adhesins PavB and PspC Are Important for the Interplay with Human Thrombospondin-1.The Journal of biological chemistry · 2015Article
- Attenuation of the phosphatidylinositol 3-kinase/Akt signaling pathway by Porphyromonas gingivalis gingipains RgpA, RgpB, and Kgp.The Journal of biological chemistry · 2015Article
- Klebsiella pneumoniae translocates across the intestinal epithelium via Rho GTPase- and phosphatidylinositol 3-kinase/Akt-dependent cell invasion.Infection and immunity · 2015Article
- Streptococcus pneumoniae ClpL modulates adherence to A549 human lung cells through Rap1/Rac1 activation.Infection and immunity · 2014Article
- Protection against epithelial damage during Candida albicans infection is mediated by PI3K/Akt and mammalian target of rapamycin signaling.The Journal of infectious diseases · 2014Article
- Bacterial factors exploit eukaryotic Rho GTPase signaling cascades to promote invasion and proliferation within their host.Small GTPases · 2014Review
- Article
- Streptococcus pneumoniae endopeptidase O (PepO) is a multifunctional plasminogen- and fibronectin-binding protein, facilitating evasion of innate immunity and invasion of host cells.The Journal of biological chemistry · 2013Article
- Streptococcus pneumoniae invades endothelial host cells via multiple pathways and is killed in a lysosome dependent manner.PloS one · 2013Article
- Transient activation of the PI3K-AKT pathway by hepatitis C virus to enhance viral entry.The Journal of biological chemistry · 2012Article
- Mechanistic exploration of AhR-mediated host protection against Streptococcus pneumoniae infection.International immunopharmacology · 2012Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pneumococcal surface protein C (PspC) is a major adhesin of Streptococcus pneumoniae, the cause of lobar pneumonia and invasive diseases. PspC interacts in a human-specific manner with the ectodomain of the human polymeric immunoglobulin receptor (pIgR) produced by respiratory epithelial cells. By adopting the retrograde machinery of human pIgR, this protein-protein interaction promotes colonization and transcytosis across the epithelial layer. Here, we explored the role of Rho family guanosine triphosphatases (GTPases), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) for ingestion of pneumococci via the human pIgR. Inhibition experiments suggested that the host-cell actin microfilaments and microtubules are essential for this pneumococcal uptake mechanism. By using specific GTPase-modifying toxins, inhibitors, and GTPase expression constructs we demonstrate that Cdc42, but not Rac1 and RhoA are involved in PspC-mediated invasion of pneumococci into host cells. Accordingly, Cdc42 is time-dependently activated during ingestion of pneumococci. In addition, PI3K and Akt are essential for ingestion of pneumococci by respiratory epithelial cells via the PspC-pIgR interaction. The subunit p85alpha of PI3K and Akt was activated during the infection process. Moreover, Akt activation upon pneumococcal invasion depends on PI3K. In conclusion, our results illustrate for the first time key signaling molecules of host cells that are required for PspC-pIgR-mediated invasion of pneumococci into epithelial cells. This unique and specific bacterial entry process is dependent on the cooperation and activation of Rho family GTPase Cdc42, PI3K, and Akt.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.