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

Area of Science:

• Microbiology
• Pathogenesis
• Respiratory Medicine

Background:

• Pseudomonas aeruginosa is a major cause of hospital-acquired pneumonia, particularly in mechanically ventilated patients, with high mortality rates.
• The mechanisms by which P. aeruginosa disseminates on mucosal surfaces and invades tissue barriers remain incompletely understood.

Purpose of the Study:

• To elucidate the mechanisms of P. aeruginosa invasion and dissemination within the human respiratory epithelium.
• To investigate the roles of specific virulence factors, including cyclic di-GMP, Type 6 Secretion System (T6SS), and Type 3 Secretion System (T6SS), in P. aeruginosa lung infection.

Main Methods:

• Utilized human respiratory epithelium organoids as a model system to mimic physiological conditions of lung infection.
• Infected organoids with wild-type and mutant strains of P. aeruginosa lacking specific virulence factors.
• Observed bacterial colonization, invasion, and interaction with epithelial cells using microscopy and genetic analysis.

Main Results:

• P. aeruginosa colonization of apical surfaces is facilitated by cyclic di-GMP-dependent asymmetric division.
• Type 6 Secretion System activity promotes preferential invasion of goblet cells.
• Type 3 Secretion System activity leads to goblet cell death and expulsion, causing epithelial rupture and facilitating bacterial translocation.

Conclusions:

• P. aeruginosa employs a coordinated strategy involving cyclic di-GMP, T6SS, and T3SS to invade goblet cells and breach the epithelial barrier from within.
• These findings provide mechanistic insights into the pathogenesis of P. aeruginosa-induced lung infections, particularly hospital-acquired pneumonia.