P. aeruginosa disrupts CDC-42/ARP-2/3 mediated F-actin organization to induce intestinal deformation in C. elegans

Apico-basal polarity maintains the integrity of cortical actin cytoskeleton and regulates secretory functions in intestinal epithelium essential for barrier defense against infections. The opportunistic pathogen, Pseudomonas aeruginosa , exploits the interplay between cell polarity and cytoskeletal machineries to subvert these defenses. Mechanistic insights into such pathogen-induced cytoskeletal alterations have largely been derived from in-vitro epithelial monolayers, which may not capture the influences of multicellular physiology such as tissue mechanics, and innate immunity. Here, we show that the extracellular P. aeruginosa disrupts apical polarity in C. elegans enterocytes, leading to fragmentation of ARP-2/3 clusters and disorganization of apical F-actin. This disruption causes shedding of actin-rich vesicles into lumen and a pronounced apical deformation. Inhibition of CDC-42-mediated actin polymerization or PI3K-AKT signalling attenuated enterocyte deformation and extended the lifespan of C. elegans upon P. aeruginosa exposure. Our findings reveal a conserved strategy by which P. aeruginosa exploits cellular polarity machinery to disrupt host actin organization during extracellular infection of the intestinal epithelium.