Escherichia coli Alpha-Hemolysin HlyA Induces Host Cell Polarity Changes, Epithelial Barrier Dysfunction and Cell Detachment in Human Colon Carcinoma Caco-2 Cell Model via PTEN-Dependent Dysregulation of Cell Junctions
| Autor: | Violaine Dony, Emanuel Schulz, Roland Bücker, Oliver Nagel, Anja Fromm, Michael Schumann, Martina Schneemann, Jörg-Dieter Schulzke |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cell signaling PTEN phosphatidylinositol Health Toxicology and Mutagenesis tight junction Cell leaky gut colon carcinoma Toxicology Cell junction Article 03 medical and health sciences 0302 clinical medicine Cell polarity medicine Escherichia coli Tensin Tight junction Chemistry Cell growth cell detachment Cell biology hemolysin cell polarity 030104 developmental biology medicine.anatomical_structure Caco-2 030220 oncology & carcinogenesis Medicine epithelial barrier |
| Zdroj: | Toxins, Vol 13, Iss 520, p 520 (2021) Toxins Volume 13 Issue 8 |
| ISSN: | 2072-6651 |
| Popis: | Escherichia coli (E. coli) of the B2 phylotype reside in human and animal intestines. The bacteria possess pathogenicity factors such as α-hemolysin (HlyA) that can induce intestinal epithelial leaks. We addressed the questions which host cell processes were dysregulated by E. coli HlyA that can potentiate intestinal diseases. The colon carcinoma cell line Caco-2 was infected by HlyA+ E. coli. Cell polarity regulation was analyzed by live cell imaging for the phosphatidylinositol-4,5-bisphosphate (PIP2) abundance. In Caco-2 monolayers, transepithelial electrical resistance was measured for characterization of barrier function. Cell proliferation and separation were assessed microscopically. Epithelial regulation and cell signaling were analyzed by RNA-Seq and Ingenuity Pathway Analysis (IPA). Our main findings from E. coli HlyA toxinogenicity in the colon carcinoma cell line are that (i) PIP2 at the membrane decrease, (ii) PTEN (phosphatase and tensin homolog) inhibition leads to cell polarity changes, (iii) epithelial leakiness follows these polarity changes by disruption of cell junctions and (iv) epithelial cell detachment increases. HlyA affected pathways, e.g., the PTEN and metastasis signaling, were identified by RNA-Seq bioinformatics calculations in IPA. In conclusion, HlyA affects cell polarity, thereby inducing epithelial barrier dysfunction due to defective tight junctions and focal leak induction as an exemplary mechanism for leaky gut. |
| Databáze: | OpenAIRE |
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