ArticlePloS one2012
Effect of levels of acetate on the mevalonate pathway of Borrelia burgdorferi.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 48 citations in OpenAlex.
- Trial
- A cofactor-promiscuous HMGR from the Lyme disease pathogen illuminates diversity in bacterial isoprenoid biosynthesis.Protein science : a publication of the Protein Society · 2026Article
- Riboflavin Salvage Supports Glycolysis in Borrelia burgdorferi Through Flavin-Dependent NADMolecular microbiology · 2026Article
- Protective efficacy of mutant strains ofInfection and immunity · 2026Article
- A cofactor-promiscuous HMGR from the Lyme disease pathogen illuminates diversity in bacterial isoprenoid biosynthesis.bioRxiv : the preprint server for biology · 2026Article
- Efficacy of Purified Borrelial Lipoproteins (PBL) as an oral formulation in reducing transmission of Lyme spirochetes from reservoir hosts tobioRxiv : the preprint server for biology · 2026Article
- Role of dual specificity phosphatase 1 in influencing inflammatory pathways in macrophages modulated byFrontiers in immunology · 2026Article
- Role of Dual Specificity Phosphatase 1 (DUSP1) in influencing inflammatory pathways in macrophages modulated bybioRxiv : the preprint server for biology · 2025Article
- Identifying Opportunity Targets in Gram-Negative Pathogens for Infectious Disease Mitigation.ACS central science · 2025Review
- Current and emerging approaches for eliminatingFrontiers in microbiology · 2024Review
- Metabolic modeling predicts unique drug targets inmSystems · 2023Article
- Cholesterol Contributes to Risk, Severity, and Machine Learning-Driven Diagnosis of Lyme Disease.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Article
- Cellular and transcriptome signatures unveiled by single-cell RNA-Seq followingFrontiers in immunology · 2023Article
- Over 40 Years of Fosmidomycin Drug Research: A Comprehensive Review and Future Opportunities.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Interactions between Borrelia burgdorferi and its hosts across the enzootic cycle.Parasite immunology · 2021Review
- Borrelia peptidoglycan interacting Protein (BpiP) contributes to the fitness of Borrelia burgdorferi against host-derived factors and influences virulence in mouse models of Lyme disease.PLoS pathogens · 2021Article
- Gene Regulation and Transcriptomics.Current issues in molecular biology · 2021Article
- Unconventional Approaches to Direct Detection of Borreliosis and Other Tick Borne Illnesses: A Path Forward.Journal of cellular immunology · 2021Article
- Short-Chain Fatty Acids Alter Metabolic and Virulence Attributes of Borrelia burgdorferi.Infection and immunity · 2018Article
- Borrelia Host Adaptation Protein (BadP) Is Required for the Colonization of a Mammalian Host by the Agent of Lyme Disease.Infection and immunity · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Borrelia burgdorferi, the agent of Lyme disease, is a spirochetal pathogen with limited metabolic capabilities that survives under highly disparate host-specific conditions. However, the borrelial genome encodes several proteins of the mevalonate pathway (MP) that utilizes acetyl-CoA as a substrate leading to intermediate metabolites critical for biogenesis of peptidoglycan and post-translational modifications of proteins. In this study, we analyzed the MP and contributions of acetate in modulation of adaptive responses in B. burgdorferi. Reverse-transcription PCR revealed that components of the MP are transcribed as individual open reading frames. Immunoblot analysis using monospecific sera confirmed synthesis of members of the MP in B. burgdorferi. The rate-limiting step of the MP is mediated by HMG-CoA reductase (HMGR) via conversion of HMG-CoA to mevalonate. Recombinant borrelial HMGR exhibited a K(m) value of 132 µM with a V(max) of 1.94 µmol NADPH oxidized minute(-1) (mg protein)(-1) and was inhibited by statins. Total protein lysates from two different infectious, clonal isolates of B. burgdorferi grown under conditions that mimicked fed-ticks (pH 6.8/37°C) exhibited increased levels of HMGR while other members of the MP were elevated under unfed-tick (pH 7.6/23°C) conditions. Increased extra-cellular acetate gave rise to elevated levels of MP proteins along with RpoS, CsrA(Bb) and their respective regulons responsible for mediating vertebrate host-specific adaptation. Both lactone and acid forms of two different statins inhibited growth of B. burgdorferi strain B31, while overexpression of HMGR was able to partially overcome that inhibition. In summary, these studies on MP and contributions of acetate to host-specific adaptation have helped identify potential metabolic targets that can be manipulated to reduce the incidence of Lyme disease.
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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.