ArticleInfection and immunity2015
Cyclic di-GMP modulates gene expression in Lyme disease spirochetes at the tick-mammal interface to promote spirochete survival during the blood meal and tick-to-mammal transmission.
Article in Infection and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
68 citing papers in PubMed, 90 citations in OpenAlex.
- Metabolic regulation of the carbonyl stress pathway and methylglyoxal in Lyme disease and relapsing fever spirochetes.PLoS pathogens · 2026Article
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- Characterizing the impact of intracutaneous dissemination on host responses duringFrontiers in immunology · 2026Article
- Updates on therapeutic targeting of diguanylate cyclase for addressing bacterial infections: A comprehensive review.World journal of microbiology & biotechnology · 2025Review
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- MCP5, a methyl-accepting chemotaxis protein regulated by both the Hk1-Rrp1 and Rrp2-RpoN-RpoS pathways, is required for the immune evasion of Borrelia burgdorferi.PLoS pathogens · 2024Article
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- The plasmid-encoded members of paralogous gene family 52 are dispensable to the enzootic cycle ofInfection and immunity · 2024Article
- DnaA modulates the gene expression and morphology of the Lyme disease spirochete.bioRxiv : the preprint server for biology · 2024Article
- MCP5, a methyl-accepting chemotaxis protein regulated by both the Hk1-Rrp1 and Rrp2-RpoN-RpoS pathways, is required for the immune evasion ofbioRxiv : the preprint server for biology · 2024Article
- BadR directly represses the expression of the glycerol utilization operon in the Lyme disease pathogen.Journal of bacteriology · 2024Article
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- c-di-GMP regulates activity of the PlzA RNA chaperone from the Lyme disease spirochete.Molecular microbiology · 2023Article
- Borrelia burgdorferi Engages Mammalian Type I IFN Responses via the cGAS-STING Pathway.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- BosR and PlzA reciprocally regulate RpoS function to sustain Borrelia burgdorferi in ticks and mammals.The Journal of clinical investigation · 2023Article
- FtlA and FtlB Are Candidates for Inclusion in a Next-Generation Multiantigen Subunit Vaccine for Lyme Disease.Infection and immunity · 2022Article
- Riboflavin salvage by Borrelia burgdorferi supports carbon metabolism and is essential for survival in the tick vector.Molecular microbiology · 2022Article
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- Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Borrelia burgdorferi, the Lyme disease spirochete, couples environmental sensing and gene regulation primarily via the Hk1/Rrp1 two-component system (TCS) and Rrp2/RpoN/RpoS pathways. Beginning with acquisition, we reevaluated the contribution of these pathways to spirochete survival and gene regulation throughout the enzootic cycle. Live imaging of B. burgdorferi caught in the act of being acquired revealed that the absence of RpoS and the consequent derepression of tick-phase genes impart a Stay signal required for midgut colonization. In addition to the behavioral changes brought on by the RpoS-off state, acquisition requires activation of cyclic di-GMP (c-di-GMP) synthesis by the Hk1/Rrp1 TCS; B. burgdorferi lacking either component is destroyed during the blood meal. Prior studies attributed this dramatic phenotype to a metabolic lesion stemming from reduced glycerol uptake and utilization. In a head-to-head comparison, however, the B. burgdorferi Δglp mutant had a markedly greater capacity to survive tick feeding than B. burgdorferi Δhk1 or Δrrp1 mutants, establishing unequivocally that glycerol metabolism is only one component of the protection afforded by c-di-GMP. Data presented herein suggest that the protective response mediated by c-di-GMP is multifactorial, involving chemotactic responses, utilization of alternate substrates for energy generation and intermediary metabolism, and remodeling of the cell envelope as a means of defending spirochetes against threats engendered during the blood meal. Expression profiling of c-di-GMP-regulated genes through the enzootic cycle supports our contention that the Hk1/Rrp1 TCS functions primarily, if not exclusively, in ticks. These data also raise the possibility that c-di-GMP enhances the expression of a subset of RpoS-dependent genes during nymphal transmission.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.