Interplay between Yersinia pestis and its flea vector in lipoate metabolism |
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Authors: | Typhanie Bouvenot Amlie Dewitte Nadia Bennaceur Elizabeth Pradel Franois Pierre Sbastien Bontemps-Gallo Florent Sebbane |
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Institution: | Univ. Lille, Inserm, CNRS, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 – CIIL - Center for Infection and Immunity of Lille, F-59000 Lille, France |
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Abstract: | To thrive, vector-borne pathogens must survive in the vector’s gut. How these pathogens successfully exploit this environment in time and space has not been extensively characterized. Using Yersinia pestis (the plague bacillus) and its flea vector, we developed a bioluminescence-based approach and employed it to investigate the mechanisms of pathogenesis at an unprecedented level of detail. Remarkably, lipoylation of metabolic enzymes, via the biosynthesis and salvage of lipoate, increases the Y. pestis transmission rate by fleas. Interestingly, the salvage pathway’s lipoate/octanoate ligase LplA enhances the first step in lipoate biosynthesis during foregut colonization but not during midgut colonization. Lastly, Y. pestis primarily uses lipoate provided by digestive proteolysis (presumably as lipoyl peptides) rather than free lipoate in blood, which is quickly depleted by the vector. Thus, spatial and temporal factors dictate the bacterium’s lipoylation strategies during an infection, and replenishment of lipoate by digestive proteolysis in the vector might constitute an Achilles’ heel that is exploited by pathogens.Subject terms: Bacterial pathogenesis, Metabolism |
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