Positive feedback regulation between RpoS and BosR in the Lyme disease pathogen Article Swipe
Sajith Raghunandanan
,
Raj Priya
,
Gaofeng Lin
,
Fuad Alanazi
,
Andrew Zoss
,
Elise Warren
,
Philip E. Stewart
,
Xiuli Yang
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1128/mbio.02766-24
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1128/mbio.02766-24
In Borrelia burgdorferi , the causative agent of Lyme disease, differential gene expression is primarily governed by the alternative sigma factor RpoS (σ S ). Understanding the regulation of RpoS is crucial for elucidating how B. burgdorferi is maintained throughout its enzootic cycle. Our recent studies have shown that the homolog of Fur/PerR repressor/activator BosR functions as an RNA-binding protein that controls the rpoS mRNA stability. However, the mechanisms regulating BosR, particularly in response to host signals and environmental cues, remain largely unclear. In this study, we uncovered a positive feedback loop between RpoS and BosR, wherein RpoS post-transcriptionally regulates BosR levels. Specifically, mutation or deletion of rpoS significantly reduced BosR levels, whereas artificial induction of rpoS resulted in a dose-dependent increase in BosR levels. Notably, RpoS does not affect bosR mRNA levels but instead modulates the turnover rate of the BosR protein. Moreover, we demonstrated that environmental cues do not directly influence bosR expression but instead induce rpoS transcription and RpoS production, thereby enhancing BosR protein levels. These findings reveal a new layer of complexity in the RpoN-RpoS regulatory pathway, challenging the existing paradigm and suggesting a need to re-evaluate the factors and signals previously implicated in regulating RpoS via BosR. This study provides new insights into the intricate regulatory networks underpinning B. burgdorferi ’s adaptation and survival in its enzootic cycle. IMPORTANCE Lyme disease is the most prevalent arthropod-borne infection in the United States. The etiological agent, Borreliella (or Borrelia ) burgdorferi , is maintained in nature through an enzootic cycle involving a tick vector and a mammalian host. RpoS, the master regulator of differential gene expression, plays a crucial role in tick transmission and mammalian infection of B. burgdorferi . This study reveals a positive feedback loop between RpoS and a Fur/PerR homolog. Elucidating this regulatory network is essential for identifying potential therapeutic targets to disrupt B. burgdorferi ’s enzootic cycle. The findings also have broader implications for understanding the regulation of RpoS and Fur/PerR family in other bacteria.
Related Topics
Concepts
rpoS
Borrelia burgdorferi
Sigma factor
Biology
rpoN
Transcription (linguistics)
Cell biology
Genetics
Lyme disease
Microbiology
Gene
Gene expression
Immunology
Promoter
Antibody
Linguistics
Philosophy
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1128/mbio.02766-24
- OA Status
- gold
- Cited By
- 3
- References
- 69
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4406905841
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4406905841Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1128/mbio.02766-24Digital Object Identifier
- Title
-
Positive feedback regulation between RpoS and BosR in the Lyme disease pathogenWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-01-28Full publication date if available
- Authors
-
Sajith Raghunandanan, Raj Priya, Gaofeng Lin, Fuad Alanazi, Andrew Zoss, Elise Warren, Philip E. Stewart, Xiuli YangList of authors in order
- Landing page
-
https://doi.org/10.1128/mbio.02766-24Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1128/mbio.02766-24Direct OA link when available
- Concepts
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rpoS, Borrelia burgdorferi, Sigma factor, Biology, rpoN, Transcription (linguistics), Cell biology, Genetics, Lyme disease, Microbiology, Gene, Gene expression, Immunology, Promoter, Antibody, Linguistics, PhilosophyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
3Total citation count in OpenAlex
- Citations by year (recent)
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2025: 3Per-year citation counts (last 5 years)
- References (count)
-
69Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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