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ResearchIn-Press PreviewInfectious diseaseMicrobiology Open Access | 10.1172/JCI166710

BosR and PlzA reciprocally regulate RpoS function to sustain Borrelia burgdorferi in ticks and mammals

André A. Grassmann,1 Rafal Tokarz,2 Caroline Golino,1 Melissa A. McLain,1 Ashley M. Groshong,1 Justin D. Radolf,1 and Melissa J. Caimano1

1Department of Medicine, University of Connecticut Health Center, Farmington, United States of America

2Center for Infection and Immunity, Columbia University, New York, United States of America

Find articles by Grassmann, A. in: JCI | PubMed | Google Scholar |

1Department of Medicine, University of Connecticut Health Center, Farmington, United States of America

2Center for Infection and Immunity, Columbia University, New York, United States of America

Find articles by Tokarz, R. in: JCI | PubMed | Google Scholar

1Department of Medicine, University of Connecticut Health Center, Farmington, United States of America

2Center for Infection and Immunity, Columbia University, New York, United States of America

Find articles by Golino, C. in: JCI | PubMed | Google Scholar

1Department of Medicine, University of Connecticut Health Center, Farmington, United States of America

2Center for Infection and Immunity, Columbia University, New York, United States of America

Find articles by McLain, M. in: JCI | PubMed | Google Scholar

1Department of Medicine, University of Connecticut Health Center, Farmington, United States of America

2Center for Infection and Immunity, Columbia University, New York, United States of America

Find articles by Groshong, A. in: JCI | PubMed | Google Scholar

1Department of Medicine, University of Connecticut Health Center, Farmington, United States of America

2Center for Infection and Immunity, Columbia University, New York, United States of America

Find articles by Radolf, J. in: JCI | PubMed | Google Scholar

1Department of Medicine, University of Connecticut Health Center, Farmington, United States of America

2Center for Infection and Immunity, Columbia University, New York, United States of America

Find articles by Caimano, M. in: JCI | PubMed | Google Scholar |

Published January 17, 2023 - More info

J Clin Invest. https://doi.org/10.1172/JCI166710.
Copyright © 2023, Grassmann et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published January 17, 2023 - Version history
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Abstract

The alternative sigma 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 TBDCapSeq to compare the transcriptomes of wild-type 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 BosR, a non-canonical Fur family regulator, and the c-di-GMP effector PlzA reciprocally regulate RpoS function. BosR is required for RpoS-mediated transcription activation and repression in addition to its well-defined role promoting RpoN-dependent transcription of rpoS. During transmission, liganded-PlzA antagonizes RpoS-mediated repression, presumably acting through BosR.  

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Version history
  • Version 1 (January 17, 2023): In-Press Preview
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