In this manuscript, we show that a TNF-like innate immune pathway expressed in enteroendocrine cells is co-opted by commensal bacteria in the intestine to activate expression of enteroendocrine peptides. For a further description of the work, see the BCH vector blog. Manuscript link
In this publication, we show that our sublingual vaccine platform can be engineered to constitutively synthesize the attenuated cholera toxin-based adjuvant mmCT in situ leading to boosting of the mucosal immune response.
Here Liao and colleagues describe an antigen presentation platform based on fusion of antigens to the Vibrio cholerae biofilm matrix protein RbmA with delivery in the form of a whole cell, live-attenuated vaccine. We show that fusion of the B subunit of cholera toxin (CTB) to RbmA and presentation via sublingual delivery of whole cells results in a mucosal immune response to both the V. cholerae O-antigen and CTB.
The Vibrio cholerae quorum sensing master regulator HapR represses virulence factor expression and biofilm formation at high cell density. In this manuscript, we show that V. cholerae quorum sensing decreases pathogen virulence in the model arthropod, Drosophila melanogaster. We show that this decrease in virulence can be attributed to repression of succinate uptake by HapR. Infection with a HapR mutant results in depletion of host lipid stores and host death. Dietary supplementation with succinate allows the host to retain its lipid stores, thus prolonging survival.
Mammalian and arthropod hosts depend on the metabolic signals generated by intestinal bacteria to maintain homeostasis. While pathogens can disrupt homeostasis by consuming these metabolic signals, our study reveals a novel role for V. cholerae quorum sensing in repressing bacterial consumption of succinate to ensure nutritional cooperation of this pathogen with its arthropod host.
Vanhove AS, Hang S, Vijayakumar V, Wong CN, Asara JM, Watnick PI.
Using the fly as a model, Audrey Vanhove and Saiyu Hang have discovered a novel virulence mechanism of intestinal pathogens in which consumption of dietary methionine sulfoxide by V. cholerae liberates host methionine sulfoxide reductase to repair oxidized host intestinal proteins required for virulence.