Coupled induction of prophage and virulence factors during tick transmission of the Lyme disease spirochete

Jenny Wachter (), Britney Cheff, Chad Hillman, Valentina Carracoi, David W. Dorward, Craig Martens, Kent Barbian, Glenn Nardone, L. Renee Olano, Margie Kinnersley, Patrick R. Secor and Patricia A. Rosa
Additional contact information
Jenny Wachter: National Institutes of Health
Britney Cheff: National Institutes of Health
Chad Hillman: National Institutes of Health
Valentina Carracoi: National Institutes of Health
David W. Dorward: National Institutes of Health
Craig Martens: National Institutes of Health
Kent Barbian: National Institutes of Health
Glenn Nardone: National Institutes of Health
L. Renee Olano: National Institutes of Health
Margie Kinnersley: The University of Montana
Patrick R. Secor: The University of Montana
Patricia A. Rosa: National Institutes of Health

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract The alternative sigma factor RpoS plays a central role in the critical host-adaptive response of the Lyme disease spirochete, Borrelia burgdorferi. We previously identified bbd18 as a negative regulator of RpoS but could not inactivate bbd18 in wild-type spirochetes. In the current study we employed an inducible bbd18 gene to demonstrate the essential nature of BBD18 for viability of wild-type spirochetes in vitro and at a unique point in vivo. Transcriptomic analyses of BBD18-depleted cells demonstrated global induction of RpoS-dependent genes prior to lysis, with the absolute requirement for BBD18, both in vitro and in vivo, circumvented by deletion of rpoS. The increased expression of plasmid prophage genes and the presence of phage particles in the supernatants of lysing cultures indicate that RpoS regulates phage lysis-lysogeny decisions. Through this work we identify a mechanistic link between endogenous prophages and the RpoS-dependent adaptive response of the Lyme disease spirochete.

Date: 2023
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DOI: 10.1038/s41467-023-35897-3

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