Activation of Vibrio cholerae quorum sensing promotes survival of an arthropod host

Abstract

Vibrio cholerae colonizes the human terminal ileum to cause cholera and the arthropod intestine and exoskeleton to persist in the aquatic environment. Attachment to these surfaces is regulated by the bacterial quorum sensing signal transduction cascade, which allows bacteria to assess the density of microbial neighbors. Intestinal colonization with V. cholerae results in expenditure of host lipid stores in the model arthropod Drosophila melanogaster. Here we report that activation of quorum sensing in the Drosophila intestine retards this process by repressing V. cholerae succinate uptake. Increased host access to intestinal succinate mitigates infection-induced lipid wasting to extend survival of V. cholerae-infected flies. Therefore, quorum sensing promotes a more favorable interaction between V. cholerae and an arthropod host by reducing the nutritional burden of intestinal colonization.

Vibrio cholerae-Symbiont Interactions Inhibit Intestinal Repair in Drosophila

“…In contrast to our studies, several strains of C6706 cause limited disease in flies and fail to block epithelial renewal (Kamareddine et al, 2018). We speculate that this is a function of differences in quorum sensing between the C6706 strains used in the respective studies, as the strain of C6706 used in this work has a low expression of the quorum-sensing mater regulator HapR (Fast et al, 2018a;Stutzmann and Blokesch, 2016), and HapR mutations convert non-pathogenic strains to lethal strains that have the ability to block IPC growth (Kamareddine et al, 2018). We believe that the fly will serve as an excellent model to identify the extent to which T6SS activity modifies the disease phenotypes described above.…”

“…The ability of V. cholerae to suppress epithelial renewal is reversed by the mutational inactivation of IMD (Wang et al, 2013), suggesting functional links between immune activity and IPC growth in infected flies. In contrast to our studies, several strains of C6706 cause limited disease in flies and fail to block epithelial renewal (Kamareddine et al, 2018). We speculate that this is a function of differences in quorum sensing between the C6706 strains used in the respective studies, as the strain of C6706 used in this work has a low expression of the quorum-sensing mater regulator HapR (Fast et al, 2018a;Stutzmann and Blokesch, 2016), and HapR mutations convert non-pathogenic strains to lethal strains that have the ability to block IPC growth (Kamareddine et al, 2018).…”

“…For example, the gut is sensitive to growth cues received or generated through host-microbe interactions (Broderick et al, 2014;Buchon et al, 2009b;Jones et al, 2013;Shin et al, 2011), raising the possibility that V. cholerae prevents IPC proliferation by modifying microbiota-derived pro-growth cues. Consistent with this hypothesis, other studies have documented the effects of V. cholerae on the availability of microbial metabolites with downstream effects on epithelial renewal (Kamareddine et al, 2018;Vanhove et al, 2017). It will be interesting to determine whether the T6SS affects the bioavailability of microbiota-derived metabolites.…”

“…IMD pathway mutants have extended viability after infection with V. cholerae, implicating host immune activity in the pathogenesis of the bacteria (Berkey et al, 2009). At the same time, infections with V. cholerae affect intestinal levels of acetate (Hang et al, 2014), succinate (Kamareddine et al, 2018), and methionine sulfoxide (Vanhove et al, 2017), with consequences for host insulin signaling, lipid homeostasis, and epithelial renewal in the host. The ability of V. cholerae to suppress epithelial renewal is reversed by the mutational inactivation of IMD (Wang et al, 2013), suggesting functional links between immune activity and IPC growth in infected flies.…”

Commensal-Pathogen Competition Impacts Host Viability

“…Combined, these results establish 6 that the T6SS contributes to V. cholerae pathogenesis in vivo. Inactivation of the T6SS does not abolish pathogenesis, suggesting that V. cholerae employs additional virulence factors such as cholera toxin, metabolite production, and quorum sensing 22,32,33 to kill the host in a T6SS-independent manner.…”