Pseudomonas aeruginosa breaches respiratory epithelia through goblet cell invasion in a microtissue model.
A Leoni SwartBenoît-Joseph LaventieRosmarie SütterlinTina JunneLuisa LauerPablo ManfrediSandro JakoniaXiao YuEvdoxia KaragkioziRusudan OkujavaUrs JenalPublished in: Nature microbiology (2024)
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.
Keyphrases
- biofilm formation
- pseudomonas aeruginosa
- cell cycle arrest
- cell death
- escherichia coli
- induced apoptosis
- cystic fibrosis
- staphylococcus aureus
- candida albicans
- end stage renal disease
- acinetobacter baumannii
- healthcare
- endothelial cells
- ejection fraction
- peritoneal dialysis
- newly diagnosed
- intensive care unit
- cardiovascular disease
- induced pluripotent stem cells
- oxidative stress
- cardiovascular events
- early onset
- pi k akt
- single cell
- acute respiratory distress syndrome
- prognostic factors
- coronary artery disease
- chronic kidney disease
- respiratory tract
- wild type