A pore-forming toxin monalysin contributes to infection-induced suppression of defecation in female Drosophila

Pathogen expulsion from the gut via defecation is an important defence strategy against infection. The microbial factors that can subvert this defence reaction remain poorly understood. While many microbes have been found to increase host intestinal peristalsis, Pseudomonas entomophila infection in Drosophila melanogaster leads to infection-induced defecation blockage, particularly in females. Here, we show that this phenotype is driven by a secreted, thermosensitive protein regulated by the GacS/GacA two-component system. Proteomic comparison of the ΔgacA mutant, which only partially inhibits defecation, and the avirulent Δhfq mutant lacking RNA chaperon Hfq, which still triggers the phenotype, identified pore-forming toxin Monalysin as one of the candidate factors required for inhibiting defecation. Consistent with these findings, the Monalysin-deficient mutant failed to fully suppress defecation and exhibited attenuated virulence and reduced persistence in the gut. Hence, Monalysin besides causing intestinal damage, has a previously unknown role in suppressing defecation and pathogen expulsion. Overall, our study identified a bacterial factor that rapidly reduces defecation frequency, consistent with transient suppression of intestinal transit, thus advancing our understanding of pathogen strategies used to subvert host defences.