The lectin LecB induces patches with basolateral characteristics at the apical membrane to promote pseudomonas aeruginosa host cell invasion
Abstract: The opportunistic bacterium Pseudomonas aeruginosa can infect mucosal tissues of the human body. To persist at the mucosal barrier, this highly adaptable pathogen has evolved many strategies, including invasion of host cells. Here, we show that the P. aeruginosa lectin LecB binds and cross-links fucosylated receptors at the apical plasma membrane of epithelial cells. This triggers a signaling cascade via Src kinases and phosphoinositide 3-kinase (PI3K), leading to the formation of patches enriched with the basolateral marker phosphatidylinositol (3,4,5)-trisphosphate (PIP3) at the apical plasma membrane. This identifies LecB as a causative bacterial factor for activating this well-known host cell response that is elicited upon apical binding of P. aeruginosa. Downstream from PI3K, Rac1 is activated to cause actin rearrangement and the outgrowth of protrusions at the apical plasma membrane. LecB-triggered PI3K activation also results in aberrant recruitment of caveolin-1 to the apical domain. In addition, we reveal a positive feedback loop between PI3K activation and apical caveolin-1 recruitment, which provides a mechanistic explanation for the previously observed implication of caveolin-1 in P. aeruginosa host cell invasion. Interestingly, LecB treatment also reversibly removes primary cilia. To directly prove the role of LecB for bacterial uptake, we coated bacterium-sized beads with LecB, which drastically enhanced their endocytosis. Furthermore, LecB deletion and LecB inhibition with l-fucose diminished the invasion efficiency of P. aeruginosa bacteria. Taken together, the results of our study identify LecB as a missing link that can explain how PI3K signaling and caveolin-1 recruitment are triggered to facilitate invasion of epithelial cells from the apical side by P. aeruginosa
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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mBio. - 13, 3 (2022) , e00819-22, ISSN: 2150-7511
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2022
- Creator
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Thünauer, Roland
Kühn, Katja
Guo, Yubing
Kotsis, Fruzsina
Xu, Maokai
Trefzer, Anne
Altmann, Silke
Wehrum, Sarah
Heshmatpour, Najmeh
Faust, Brian
Landi, Alessia
Diedrich, Britta
Dengjel, Jörn
Kühn, Ernst Wolfgang
Imberty, Anne
Römer, Winfried
- DOI
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10.1128/mbio.00819-22
- URN
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urn:nbn:de:bsz:25-freidok-2268755
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:31 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Thünauer, Roland
- Kühn, Katja
- Guo, Yubing
- Kotsis, Fruzsina
- Xu, Maokai
- Trefzer, Anne
- Altmann, Silke
- Wehrum, Sarah
- Heshmatpour, Najmeh
- Faust, Brian
- Landi, Alessia
- Diedrich, Britta
- Dengjel, Jörn
- Kühn, Ernst Wolfgang
- Imberty, Anne
- Römer, Winfried
- Universität
Time of origin
- 2022