ArticleDrug design, development and therapy2015
Borreliacidal activity of Borrelia metal transporter A (BmtA) binding small molecules by manganese transport inhibition.
Article in Drug design, development and therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
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- CspZ variant-specific interaction with factor H incorporates a metal site to support Lyme borreliae complement evasion.The Journal of biological chemistry · 2025Article
- Current and emerging approaches for eliminatingFrontiers in microbiology · 2024Review
- Superior efficacy of combination antibiotic therapy versus monotherapy in a mouse model of Lyme disease.Frontiers in microbiology · 2023Article
- Contribution of a ZIP-family protein to manganese uptake and infective endocarditis virulence in Streptococcus sanguinis.Molecular microbiology · 2022Article
- Lyme Disease Pathogenesis.Current issues in molecular biology · 2021Review
- Gene Regulation and Transcriptomics.Current issues in molecular biology · 2021Article
- "Repurposing" Disulfiram in the Treatment of Lyme Disease and Babesiosis: Retrospective Review of First 3 Years' Experience in One Medical Practice.Antibiotics (Basel, Switzerland) · 2020Article
- Repurposing Disulfiram (Tetraethylthiuram Disulfide) as a Potential Drug Candidate againstAntibiotics (Basel, Switzerland) · 2020Article
- Establishment of an in vitro RNA polymerase transcription system: a new tool to study transcriptional activation in Borrelia burgdorferi.Scientific reports · 2020Article
- Azlocillin can be the potential drug candidate against drug-tolerant Borrelia burgdorferi sensu stricto JLB31.Scientific reports · 2020Article
- Complement Evasion inAntibiotics (Basel, Switzerland) · 2019Review
- Disulfiram (Tetraethylthiuram Disulfide) in the Treatment of Lyme Disease and Babesiosis: Report of Experience in Three Cases.Antibiotics (Basel, Switzerland) · 2019Article
- In vitro and in vivo evaluation of cephalosporins for the treatment of Lyme disease.Drug design, development and therapy · 2018Article
- Screening of NCI-DTP library to identify new drug candidates for Borrelia burgdorferi.The Journal of antibiotics · 2017Article
- Identification of new drug candidates against Borrelia burgdorferi using high-throughput screening.Drug design, development and therapy · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Borrelia burgdorferi, the causative agent of Lyme disease, utilizes manganese (Mn) for its various metabolic needs. We hypothesized that blocking Mn transporter could be a possible approach to inhibit metabolic activity of this pathogen and eliminate the infection. We used a combination of in silico protein structure prediction together with molecular docking to target the Borrelia metal transporter A (BmtA), a single known Mn transporter in Borrelia and screened libraries of FDA approved compounds that could potentially bind to the predicted BmtA structure with high affinity. Tricyclic antihistamines such as loratadine, desloratadine, and 3-hydroxydesloratadine as well as yohimbine and tadalafil demonstrated a tight binding to the in silico folded BmtA transporter. We, then, tested borreliacidal activity and dose response of the shortlisted compounds from this screen using a series of in vitro assays. Amongst the probed compounds, desloratadine exhibited potent borreliacidal activity in vitro at and above 78 μg/mL (250 μM). Borrelia treated with lethal doses of desloratadine exhibited a significant loss of intracellular Mn specifically and a severe structural damage to the bacterial cell wall. Our results support the possibility of developing a novel, targeted therapy to treat Lyme disease by targeting specific metabolic needs of Borrelia.
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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.