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Rubinic, M.

Publications and source records attributed to Rubinic, M..

3 recordsLinked to original sources

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 {Delta}gacA mutant, which does not inhibit defecation, and the avirulent {Delta}hfq 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. Consistently, the Monalysin-deficient mutant was unable to inhibit defecation. Hence, Monalysin besides causing intestinal damage, has a previously unknown role in suppressing defecation and potentially 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.

microbiology↗

Infection-Induced Elevation of Gut Glycosaminoglycans Fosters Microbiota Expansion in Drosophila melanogaster

While host genetics influence the composition of intestinal microbial communities, host genetic factors controlling the abundance of intestinal commensals remain to be determined. Here, we performed a genome-wide association (GWA) study in the fruit fly Drosophila melanogaster to identify host genetic variants linked to the abundance of Lactiplantibacillus plantarum - a major gut commensal of fruit flies. Our GWA study uncovered significant association between polymorphisms in genes involved in heparan sulfate synthesis and L. plantarum load. RNAi mediated knockdown of some of these genes resulted in reduced heparan sulfate synthesis and L. plantarum abundance. Mechanistically, heparan sulfate facilitates adhesion of L. plantarum to host epithelium and promotes biofilm formation. We further showed that infection induces heparan sulfate synthesis by the host via activation of the Nf-kB immune signaling cascade. Increased availability of heparan sulfate during infection results in the expansion of L. plantarum population in the gut and protection of the host from intestinal pathogens via colonization resistance. Furthermore, heparan sulfate is required for infection-induced expression of immune effectors and for prevention of intestinal dysplasia. These findings underscore heparan sulfate as a crucial modulator of intestinal homeostasis, pivotal in microbiota control, intestinal defense, and epithelial renewal.

microbiology↗

Sex Differences in Drosophila Intestinal Metabolism Contribute to Sexually Dimorphic Infection Outcome and Alter Gut Pathogen Virulence

Sexual dimorphism in infection outcomes is a pervasive phenomenon, the underlying mechanisms of which remain incompletely understood. Here, utilizing Pseudomonas entomophila intestinal infection in Drosophila, we demonstrated that sex differences in intestinal redox processes contribute to female bias in susceptibility to gut infection. Female inability to overcome excessive pathogen-induced oxidative stress results in defecation blockage, pathogen persistence, and host death. Male flies exhibit increased carbohydrate metabolism and pentose phosphate pathway activity - a key antioxidant defense system. This allows males to withstand oxidative stress-induced defecation blockage and clear the pathogen from the intestine, resulting in survival. Additionally, P. entomophila showed increased expression of several virulence factors, including RNA-binding protein Hfq, in the female gut, contributing to female-biased virulence of P. entomophila. Thus, the effect of the gut metabolic environment on host defenses and pathogen virulence determines the sex differences in intestinal infection outcomes. HighlightsIntestinal transit of gut pathogen contributes to sexually dimorphic susceptibility to Drosophila gut infection. Male bias in PPP favors pathogen clearance and recovery post-infection. P. entomophila reacts differently to female gut environment, where higher levels of Hfq might contribute to virulence/lethality. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/655590v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@1d6d36borg.highwire.dtl.DTLVardef@d24f2aorg.highwire.dtl.DTLVardef@14b4ed1org.highwire.dtl.DTLVardef@123b46c_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗