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; Patricia A. Rosa

doi:10.1038/s41467-023-35897-3

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, Patricia A. Rosa

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English
Article number	198
Pages (from-to)	198
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-35897-3
State	Published - Jan 13 2023

Funding

We would like to acknowledge Stacy Ricklefs and Dan Bruno for their help with RNA sequencing and Elizabeth Fischer for help with electron microscopy. We would also like to thank Ashley Groshong and Liam Fitzsimmons for their careful reviews and helpful suggestions for this manuscript. This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. PRS is supported by NIH grants R21AI151597 and P30GM140963. MK and PRS are supported by Montana INBRE (P20GM103474). We would like to acknowledge Stacy Ricklefs and Dan Bruno for their help with RNA sequencing and Elizabeth Fischer for help with electron microscopy. We would also like to thank Ashley Groshong and Liam Fitzsimmons for their careful reviews and helpful suggestions for this manuscript. This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. PRS is supported by NIH grants R21AI151597 and P30GM140963. MK and PRS are supported by Montana INBRE (P20GM103474).

Funder number
P20GM103474
R21AI151597, P30GM140963

Keywords

Animals
Bacterial Proteins/metabolism
Borrelia burgdorferi/virology
Gene Expression Regulation, Bacterial
Prophages/genetics
Sigma Factor/metabolism
Ticks/microbiology
Virulence Factors/metabolism
Host-Pathogen Interactions

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10.1038/s41467-023-35897-3

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Wachter, J., Cheff, B., Hillman, C., Carracoi, V., Dorward, D. W., Martens, C., Barbian, K., Nardone, G., Renee Olano, L., Kinnersley, M., Secor, P. R., & Rosa, P. A. (2023). Coupled induction of prophage and virulence factors during tick transmission of the Lyme disease spirochete. Nature Communications, 14(1), 198. Article 198. https://doi.org/10.1038/s41467-023-35897-3

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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.",

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AU - Rosa, Patricia A.

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KW - Virulence Factors/metabolism

KW - Host-Pathogen Interactions

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

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