ArticlePLoS pathogens2022
The glycerol-3-phosphate dehydrogenases GpsA and GlpD constitute the oxidoreductive metabolic linchpin for Lyme disease spirochete host infectivity and persistence in the tick.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 24 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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- The BosR Is Back!Molecular microbiology · 2026Article
- The CpxR-GlvR regulatory axis ofFrontiers in cellular and infection microbiology · 2026Article
- Activation of theInfection and immunity · 2025Article
- Epigenetic cellular memory inProceedings of the National Academy of Sciences of the United States of America · 2025Article
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- Analysis of the BadR regulon in Borrelia burgdorferi.BMC microbiology · 2025Article
- Adaptive immunity inApplied and environmental microbiology · 2024Article
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- Hitchhiker's Guide toJournal of bacteriology · 2024Review
- Glyoxal oxidase-mediated detoxification of reactive carbonyl species contributes to virulence, stress tolerance, and development in a pathogenic fungus.PLoS pathogens · 2024Article
- BadR directly represses the expression of the glycerol utilization operon in the Lyme disease pathogen.Journal of bacteriology · 2024Article
- Metabolic modeling predicts unique drug targets inmSystems · 2023Article
- Pathogenicity and virulence ofVirulence · 2023Review
- Antigen-Specific CD4 T Cell and B Cell Responses to Borrelia burgdorferi.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Metabolic Network Models of themSystems · 2023Article
- Riboflavin salvage by Borrelia burgdorferi supports carbon metabolism and is essential for survival in the tick vector.Molecular microbiology · 2022Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
We have identified GpsA, a predicted glycerol-3-phosphate dehydrogenase, as a virulence factor in the Lyme disease spirochete Borrelia (Borreliella) burgdorferi: GpsA is essential for murine infection and crucial for persistence of the spirochete in the tick. B. burgdorferi has a limited biosynthetic and metabolic capacity; the linchpin connecting central carbohydrate and lipid metabolism is at the interconversion of glycerol-3-phosphate and dihydroxyacetone phosphate, catalyzed by GpsA and another glycerol-3-phosphate dehydrogenase, GlpD. Using a broad metabolomics approach, we found that GpsA serves as a dominant regulator of NADH and glycerol-3-phosphate levels in vitro, metabolic intermediates that reflect the cellular redox potential and serve as a precursor for lipid and lipoprotein biosynthesis, respectively. Additionally, GpsA was required for survival under nutrient stress, regulated overall reductase activity and controlled B. burgdorferi morphology in vitro. Furthermore, during in vitro nutrient stress, both glycerol and N-acetylglucosamine were bactericidal to B. burgdorferi in a GlpD-dependent manner. This study is also the first to identify a suppressor mutation in B. burgdorferi: a glpD deletion restored the wild-type phenotype to the pleiotropic gpsA mutant, including murine infectivity by needle inoculation at high doses, survival under nutrient stress, morphological changes and the metabolic imbalance of NADH and glycerol-3-phosphate. These results illustrate how basic metabolic functions that are dispensable for in vitro growth can be essential for in vivo infectivity of B. burgdorferi and may serve as attractive therapeutic targets.
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