1. BosR and PlzA reciprocally regulate RpoS function to sustain Borrelia burgdorferi in ticks and mammals
- Author
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Grassmann, Andre A., Tokarz, Rafal, Golino, Caroline, McLain, Melissa A., Groshong, Ashley M., Radolf, Justin D., and Caimano, Melissa J.
- Subjects
Borrelia burgdorferi -- Physiological aspects -- Genetic aspects ,Transcriptional coactivators -- Physiological aspects -- Health aspects ,Disease transmission -- Physiological aspects ,Lyme disease -- Development and progression -- Causes of ,Host-parasite relationships -- Physiological aspects ,Health care industry - Abstract
The RNA polymerase alternative o factor RpoS in Borrelia burgdorferi (Bb), the Lyme disease pathogen, is responsible for programmatic-positive and -negative gene regulation essential for the spirochete's dual-host enzootic cycle. RpoS is expressed during tick-to-mammal transmission and throughout mammalian infection. Although the mammalian-phase RpoS regulon is well described, its counterpart during the transmission blood meal is unknown. Here, we used Bb- specific transcript enrichment by tick-borne disease capture sequencing (TBDCapSeq) to compare the transcriptomes of WT and [DELTA]rpoSBb in engorged nymphs and following mammalian host-adaptation within dialysis membrane chambers. TBDCapSeq revealed dramatic changes in the contours of the RpoS regulon within ticks and mammals and further confirmed that RpoS-mediated repression is specific to the mammalian-phase of Bb's enzootic cycle. We also provide evidence that RpoS-dependent gene regulation, including repression of tick-phase genes, is required for persistence in mice. Comparative transcriptomics of engineered Bb strains revealed that the Borrelia oxidative stress response regulator (BosR), a noncanonical Fur family member, and the cyclic diguanosine monophosphate (c-di- GMP) effector PlzA reciprocally regulate the function of RNA polymerase complexed with RpoS. BosR is required for RpoS- mediated transcription activation and repression in addition to its well-defined role promoting transcription of rpoS by the RNA polymerase alternative o factor RpoN. During transmission, ligand-bound PlzA antagonizes RpoS-mediated repression, presumably acting through BosR., Introduction Lyme disease (LD) is a multisystem infectious disorder caused by the highly motile, invasive spirochetal pathogen Borrelia burgdorferi (Bb) (1). With an estimated 476,000 cases diagnosed and treated annually, [...]
- Published
- 2023
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