Pseudomonas aeruginosa: associated pathogenesis, epidemiology, resistance mechanisms, host response and emerging...

Pseudomonas aeruginosa is recognized as a critical-priority pathogen due to its major role in healthcare-associated infections (HAIs) and the rapid global rise of multidrug resistance. It is responsible for approximately 7.1-7.3% of HAIs worldwide and up to 23% of intensive care unit infections, specifically ventilator-associated pneumonia, where mortality can reach 32-42.8%. In chronic lung diseases, especially cystic fibrosis, P. aeruginosa commonly becomes the dominant pathogen in adulthood and contributes to progressive lung function decline. A major factor supporting long-term survival is biofilm formation, which can increase antimicrobial tolerance by up to 1000-fold compared with free-living bacteria. Virulence is further regulated through coordinated production of phenazines, rhamnolipids, exopolysaccharides, and quorum sensing signalling systems. The toxin pyocyanin, produced by 90-95% of clinical isolates, damages host tissues by disrupting cellular respiration, impairing ciliary activity, disturbing calcium balance, and promoting neutrophil apoptosis. During chronic infection, host defence mechanisms, including epithelial barriers, mucociliary clearance (~90% removal of inhaled particles), antimicrobial peptides, and immune cell responses, become less effective, while biofilms promote persistent inflammation and poor bacterial clearance. Increasing multidrug and carbapenem resistance (up to 47.6% in Europe and 32.8% in Asia) is driving interest in alternative therapies, including anti virulence agents, biofilm-disrupting enzymes, nanoparticles, bacteriophage therapy, and host-directed approaches targeting excessive inflammatory responses.