Pseudomonas aeruginosa breaches respiratory epithelia through goblet cell invasion in a microtissue model.

Autor: Swart AL; Biozentrum, University of Basel, Basel, Switzerland., Laventie BJ; Biozentrum, University of Basel, Basel, Switzerland., Sütterlin R; Biozentrum, University of Basel, Basel, Switzerland., Junne T; Biozentrum, University of Basel, Basel, Switzerland., Lauer L; Biozentrum, University of Basel, Basel, Switzerland., Manfredi P; Biozentrum, University of Basel, Basel, Switzerland., Jakonia S; Biozentrum, University of Basel, Basel, Switzerland., Yu X; Cardiovascular, Metabolism, Immunology, Infectious Diseases and Ophthalmology (CMI2O), Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland., Karagkiozi E; Cardiovascular, Metabolism, Immunology, Infectious Diseases and Ophthalmology (CMI2O), Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland., Okujava R; Cardiovascular, Metabolism, Immunology, Infectious Diseases and Ophthalmology (CMI2O), Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland., Jenal U; Biozentrum, University of Basel, Basel, Switzerland. urs.jenal@unibas.ch.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2024 Jul; Vol. 9 (7), pp. 1725-1737. Date of Electronic Publication: 2024 Jun 10.
DOI: 10.1038/s41564-024-01718-6
Abstrakt: Pseudomonas aeruginosa, a leading cause of severe hospital-acquired pneumonia, causes infections with up to 50% mortality rates in mechanically ventilated patients. Despite some knowledge of virulence factors involved, it remains unclear how P. aeruginosa disseminates on mucosal surfaces and invades the tissue barrier. Using infection of human respiratory epithelium organoids, here we observed that P. aeruginosa colonization of apical surfaces is promoted by cyclic di-GMP-dependent asymmetric division. Infection with mutant strains revealed that Type 6 Secretion System activities promote preferential invasion of goblet cells. Type 3 Secretion System activity by intracellular bacteria induced goblet cell death and expulsion, leading to epithelial rupture which increased bacterial translocation and dissemination to the basolateral epithelium. These findings show that under physiological conditions, P. aeruginosa uses coordinated activity of a specific combination of virulence factors and behaviours to invade goblet cells and breach the epithelial barrier from within, revealing mechanistic insight into lung infection dynamics.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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