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

Abstract

Apico-basal polarity is essential for maintaining cytoskeletal organization and regulating transport and secretory functions in the intestinal epithelium. The opportunistic pathogen Pseudomonas aeruginosa exploits the interactions between cell polarity and cytoskeletal networks to promote infection. However, most mechanistic insights into these processes have come from in-vitro epithelial monolayers, which do not fully capture the complexity of multicellular tissues. Here, we show that heat-labile factor/s secreted by P. aeruginosa disrupt apical polarity in Caenorhabditis elegans enterocytes through a PI3K-AKT-dependent mechanism. This disruption is accompanied by apical enrichment of PI(3,4,5)P3, fragmentation of ARP-2/3 organization, localized disruption of apical F-actin, release of F-actin-rich vesicles into the intestinal lumen, and pronounced deformation of the apical surface. Perturbing CDC-42-ARP-2/3-dependent actin assembly, PI3K-AKT signalling, or the endotube regulators, IFB-2 and IFO-1 suppressed intestinal deformation and significantly extend host survival following P. aeruginosa exposure. Notably, these changes occured without detectable loss of epithelial tissue integrity. Together, our findings identify epithelial polarity disruption as a mechanism through which extracellular P. aeruginosa remodels the host cytoskeleton and alters tissue mechanics during infection.