Nutrient-dependent gene regulation in the agent of Lyme disease

Lin, Ying-Han
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Borrelia burgdorferi(Bb) is the causative agent of Lyme disease, a vector-borne illness transmitted to vertebrate hosts by infected Ixodes spp. ticks. Bb transitions from tick vector to vertebrate host by altering its gene expression in response to highly disparate, host-specific environmental cues. Bb is highly host-adapted, and has limited metabolic capabilities; understanding the link between metabolism and virulence will help develop novel strategies to reduce the pathogen burden in reservoir hosts, thus reducing the incidence of Lyme disease. We focused on three aspects of the acetate utilization pathway to link metabolism and virulence in Bb: two of the major enzymes involved in the acetate utilization pathway; acetate kinase (AckA) and phosphate acetyltransferase (Pta); and the effects of Short-chain Fatty Acids (SCFAs) on host-specific adaptation of Bb were investigated. We found that ackA is essential for the survival of Bb in vitro and in the murine model of Lyme disease. Furthermore, Pta was down-regulated in an ackA mutant strain under tick specific conditions. We also observed the up-regulation of vertebrate specific determinants such as RpoS, OspC, and DbpA regardless of the in vitro growth condition in a modified csrABb strain (8S) carrying a borrelial shuttle vector overexpressing Pta. Lastly, we focused on the effects of key metabolites including acetate, propionate, and butyrate on the activation of the Rrp2-RpoN-RpoS pathway: increasing SCFAs under in vitro growth conditions resulted in increased levels of vertebrate specific determinants thus, linking metabolism and the activation of the virulence factors in Bb.

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acetate, Borrelia, gene, biological science
Integrative Biology