Artikel ; Online: BosR and PlzA reciprocally regulate RpoS function to sustain Borrelia burgdorferi in ticks and mammals.
The Journal of clinical investigation
2023 Band 133, Heft 5
Abstract: The RNA polymerase alternative σ 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 ...
| Abstract | The RNA polymerase alternative σ 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 ΔrpoS Bb 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 σ factor RpoN. During transmission, ligand-bound PlzA antagonizes RpoS-mediated repression, presumably acting through BosR. |
|---|---|
| Mesh-Begriff(e) | Mice ; Animals ; Borrelia burgdorferi/genetics ; Borrelia/metabolism ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Ticks/genetics ; Sigma Factor/genetics ; Sigma Factor/metabolism ; Lyme Disease/genetics ; Mammals/metabolism ; Gene Expression Regulation, Bacterial |
| Chemische Substanzen | Bacterial Proteins ; Sigma Factor |
| Sprache | Englisch |
| Erscheinungsdatum | 2023-03-01 |
| Erscheinungsland | United States |
| Dokumenttyp | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 3067-3 |
| ISSN | 1558-8238 ; 0021-9738 |
| ISSN (online) | 1558-8238 |
| ISSN | 0021-9738 |
| DOI | 10.1172/JCI166710 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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