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.

为了茁壮成长，媒介传播的病原体必须在媒介的肠道中存活。这些病原体如何在时间和空间上成功利用这种环境尚未得到广泛表征。使用鼠疫耶尔森氏菌（鼠疫杆菌）及其跳蚤载体，我们开发了一种基于生物发光的方法，并用它以前所未有的详细程度研究发病机制。值得注意的是，代谢酶的脂酰化，通过硫辛酸的生物合成和回收，增加了跳蚤对鼠疫耶尔森氏菌的传播率。有趣的是，补救途径的硫辛酸/辛酸连接酶 LplA 在前肠定植期间增强了硫辛酸生物合成的第一步，但在中肠定植期间没有。最后，鼠疫耶尔森氏菌主要使用消化蛋白水解提供的硫辛酸（可能是脂酰肽），而不是血液中的游离硫辛酸，后者会很快被载体耗尽。因此，空间和时间因素决定了细菌在感染期间的脂肪化策略，载体中通过消化蛋白水解补充脂肪酸可能构成被病原体利用的致命弱点。