Autophagy in Pseudomonas aeruginosa infection: host defense, bacterial countermeasures, and therapeutic targeting

Pseudomonas aeruginosa ( P. aeruginosa ) is a major opportunistic pathogen whose diverse virulence strategies, increasing antibiotic resistance, and ability to establish persistent infections continue to compromise the efficacy of conventional antimicrobial therapies. Although traditionally regarded as an extracellular pathogen, P. aeruginosa can also enter and persist within host cells, triggering inflammatory responses and cellular injury while simultaneously modulating host autophagic responses. On the one hand, xenophagy and related autophagic processes recognize and deliver intracellular bacteria for lysosomal degradation. Mitophagy eliminates damaged mitochondria generated during infection and limits the accumulation of mitochondrial danger signals. Meanwhile, autophagy regulates inflammasome activation by controlling the removal of damaged organelles and inflammasome components, thereby shaping inflammatory responses during infection. Collectively, these processes contribute to the protective role of autophagy in host defense against P. aeruginosa infection. On the other hand, P. aeruginosa can interfere with or remodel host autophagy through secreted effector molecules, quorum sensing signals, and infection-induced host signaling pathways, resulting in a functional disconnect between autophagic activation and effective bacterial clearance or other antimicrobial responses. This review summarizes current advances in understanding the interplay between autophagy and P. aeruginosa , highlighting the protective functions of autophagy in host defense, the countermeasures employed by P. aeruginosa to evade autophagic clearance, and the therapeutic implications of these host–pathogen interactions. These insights may support the development of host-directed therapeutic approaches targeting autophagy to improve antibacterial defense against P. aeruginosa .