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Invasion of human epithelial cells by Pseudomonas aeruginosa involves src-like tyrosine kinases p60Src and p59Fyn
M Esen1, H Grassmé, J Riethmüller
1Department of Physiology, University of Tuebingen, 72076 Tuebingen, Germany.
Abstract:
Pseudomonas aeruginosa plays a major role in respiratory tract infections or sepsis in patients with cystic fibrosis or upon suppression of the immune system. Several P. aeruginosa strains have been shown to be internalized by human epithelial cells; however, the molecular mechanisms of the invasion process are poorly characterized. Here, we show that the internalization of P. aeruginosa into human epithelial cells results in and requires activation of the Src-like tyrosine kinases p59Fyn and p60Src and the consequent tyrosine phosphorylation of several eukaryotic proteins. The significance of Src-like tyrosine kinase activation is shown by an almost complete blockade of P. aeruginosa internalization, but not adhesion, upon inhibition of Src-like tyrosine kinases. Likewise, inhibition of P. aeruginosa binding to CFTR, which has been shown to block P. aeruginosa internalization, prevents Src and Fyn activation, supporting a pivotal role of Src-like tyrosine kinases for invasion by P. aeruginosa.
Insights
Pseudomonas aeruginosa invasion into human cells requires Src-like tyrosine kinases (Src and Fyn). Inhibiting these kinases blocks bacterial entry but not adhesion, revealing a key mechanism in infection.
Area of Science:
- Microbiology
- Cell Biology
- Biochemistry
Background:
- Pseudomonas aeruginosa is a significant pathogen in cystic fibrosis and immunocompromised patients.
- Bacterial internalization by host cells is crucial for infection but poorly understood.
- P. aeruginosa is known to be internalized by human epithelial cells.
Purpose of the Study:
- To elucidate the molecular mechanisms of P. aeruginosa internalization into human epithelial cells.
- To investigate the role of Src-like tyrosine kinases in bacterial invasion.
Main Methods:
- Studied P. aeruginosa internalization in human epithelial cells.
- Investigated the activation of Src-like tyrosine kinases (p59Fyn and p60Src).
- Utilized kinase inhibitors to assess the impact on bacterial internalization and adhesion.
Main Results:
- P. aeruginosa internalization triggers Src and Fyn activation and protein tyrosine phosphorylation.
- Inhibition of Src-like tyrosine kinases significantly blocked bacterial internalization, but not adhesion.
- Blocking P. aeruginosa binding to CFTR also prevented Src and Fyn activation.
Conclusions:
- Src-like tyrosine kinases (Src and Fyn) are essential for P. aeruginosa invasion into human epithelial cells.
- These kinases play a pivotal role in the internalization process, distinct from bacterial adhesion.
- Targeting Src-like tyrosine kinases may offer a strategy to combat P. aeruginosa infections.