Molecular entry mechanism(s) of Pseudomonas aeruginosa : : impact of Abl kinase, LecA and Gb3

Abstract: Pseudomonas aeruginosa is a Gram-negative opportunistic human pathogen. It is capable of causing severe infections of the respiratory tract, urinary tract, skin and eyes, especially chronic infections in the lungs of patients with cystic fibrosis leading to damage of the lung epithelium, decline in lung function and death. Internalization of P. aeruginosa by host cells significantly contributes to its pathogenicity. The entry mechanism(s), the bacterial factors and the host cell factors involved in this process are incompletely understood. The non-receptor Abelson tyrosine kinase (Abl) has been shown to be engaged by P. aeruginosa to promote its internalization into host cells. The host glycosphingolipid globotriaosylceramide (also known as Gb3), representing a host signalling receptor, interacts with the galactophilic lectin LecA, one of the virulence factors produced by P. aeruginosa, triggering membrane engulfment of P. aeruginosa at the initial stage of entry into human lung epithelial cells. So far, the bacterial factors as well as the host cell receptors, which activate Abl kinase signalling during P. aeruginosa invasion, remain elusive.
In particular, H1299 human lung epithelial cells, Chinese hamster ovary (CHO) cells, the P. aeruginosa wild type strain PAO1, PAO1 LecA knockout mutant (ΔlecA) and GFP-tagged PAO1 were employed to study the invasion signalling process of P. aeruginosa into host cells by using microbiological, biochemical and cell biological approaches.
The results suggest that Abl kinase activity is required and induced during P. aeruginosa efficient entry into H1299 cells. LecA significantly triggers Abl kinase activity even at nanomolar concentrations in H1299 cells. Both, inhibition of Gb3 expression and LecA function, reduced Abl-dependent phosphorylation of the adaptor protein CrkII at tyrosine 221, remarkably. Ectopic expression of Gb3 in CHO cells sensitized these cells for LecA-induced Abl activation. Moreover, Src family kinases have been linked to LecA-Gb3 mediated Abl activation.
In summary, the project identified a glycolipid receptor, Gb3, for Abl kinase activation, and demonstrated a yet undescribed role for LecA as an Abl activator during the cell entry stage of P. aeruginosa. LecA-Gb3 interactions induce Abl-dependent signalling during bacterial entry into host cells. Hence, this lectin-GSL complex may represent and be further exploited as a potential target for drug development of an antibacterial therapy against P. aeruginosa

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Universität Freiburg, Dissertation, 2016

Klassifikation und Themen

• Schlagwort: Pseudomonas aeruginosa ; Pseudomonas ; Cells ; Pseudomonas aeruginosa

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2016
• Urheber: Zheng, Shuangshuang
• Beteiligte Personen und Organisationen: Römer, Winfried ; Albert-Ludwigs-Universität Freiburg. Fakultät für Biologie

Weitere Informationen

• DOI: 10.6094/UNIFR/11277
• URN: urn:nbn:de:bsz:25-freidok-112773
• Rechteinformation: Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 25.03.2025, 13:51 MEZ