Author: pwatnick

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Fernanda reviews the complex interaction between sex steroids, the innate immune response, and the microbiota in the mammalian intestine! DOI: 10.1016/j.tim.2020.11.001

Methionine availability in the arthropod intestine is elucidated through identification of Vibrio cholerae methionine acquisition systems.

An approach to understanding conditions in the host intestine by defining pathogen nutrient uptake systems.

Audrey S. Vanhove, Bat-Erdene Jugder, Daniela Barraza, and Paula I. Watnick

DOI: 10.1128/AEM.00371-20

Hypothesis: Microbes activate mechanical, metabolic, and antibacterial branches of the IMD pathway in enteroendocrine cells of the Drosophila anterior midgut.

The phosphoenolpyruvate phosphotransferase system (PTS) is a phosphotransfer cascade that regulates bacterial metabolism, behavior, and the transport of many sugars.  Glucose-specific enzyme IIA (EllAGlc) is component of the PTS that carries out phosphotransfer and regulates both membrane-associated and cytoplasmic partners through direct protein-protein interactions.  Here Vijayakumar et al identify an amphipathic helix at the N-terminus of Vibrio cholerae EIIAGlc that enables this protein to associate with the inner membrane.  This amphipathic helix is essential for EIIAGlc regulation of membrane-associated partners, and Dr. Vijayakumar shows that unrelated amphipathic helices can rescue function.  Removal of this amphipathic helix uncouples phosphotransfer through the PTS from sugar transport.  Finally, Dr. Vijayakumar shows that EIIAGlc regulates opposing cytoplasmic  and membrane-associated regulators of biofilm formation and bacterial metabolism in the mammalian intestine whose activities may be studied in isolation by removal of the amphipathic helix.

https://mbio.asm.org/content/9/5/e00858-18.long

The EIIAGlc amphipathic helix

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.

manuscript link

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.

manuscript link