Evidence map›Paper›PMID 33214838›Full record

ArticleACS medicinal chemistry letters2020

Dual-Target Inhibitors of the Folate Pathway Inhibit Intrinsically Trimethoprim-Resistant DfrB Dihydrofolate Reductases.

Jacynthe L Toulouse, Genbin Shi, Claudèle Lemay-St-Denis, Maximilian C C J C Ebert, Daniel Deon, Marc Gagnon, Edward Ruediger, Kévin Saint-Jacques, Delphine Forge, Jean Jacques Vanden Eynde and 3 more

Open access · greenAbstract read
In one paragraph

Article in ACS medicinal chemistry letters, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.3field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Flourishing Antibacterial Strategies for Osteomyelitis Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Review
  4. A conserved SH3-like fold in diverse putative proteins tetramerizes into an oxidoreductase providing an antimicrobial resistance phenotype.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Frontiers in microbiology · 2021
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

Jacynthe L ToulouseDépartement de biochimie, Université de Montréal, Montréal, Quebec H3T 1J4, Canada.
Genbin ShiMacromolecular Crystallography Laboratory, NCI, Frederick, Maryland 21702, United States.
Claudèle Lemay-St-DenisDépartement de biochimie, Université de Montréal, Montréal, Quebec H3T 1J4, Canada.
Maximilian C C J C EbertChemical Computing Group ULC, Montréal, Quebec H3A 2R7, Canada.
Daniel DeonInstitute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Quebec H3T 1J4, Canada.
Marc GagnonInstitute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Quebec H3T 1J4, Canada.
Edward RuedigerInstitute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Quebec H3T 1J4, Canada.
Kévin Saint-JacquesDépartement de chimie, Université de Sherbrooke, Sherbrooke, Quebec J1K 2R1, Canada.
Delphine ForgeLaboratoire de chimie organique, Université de Mons, 7000 Mons, Belgium.
Jean Jacques Vanden EyndeLaboratoire de chimie organique, Université de Mons, 7000 Mons, Belgium.
Anne MarinierInstitute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Quebec H3T 1J4, Canada.
Xinhua JiMacromolecular Crystallography Laboratory, NCI, Frederick, Maryland 21702, United States.
Joelle N PelletierDépartement de biochimie, Université de Montréal, Montréal, Quebec H3T 1J4, Canada.
Institute for Research in Immunology and Cancer · CACentre in Green Chemistry and Catalysis · CAUniversity of Mons · BEUniversité de Sherbrooke · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Trimethoprim (TMP) is widely used to treat infections in humans and in livestock, accelerating the incidence of TMP resistance. The emergent and largely untracked type II dihydrofolate reductases (DfrBs) are intrinsically TMP-resistant plasmid-borne Dfrs that are structurally and evolutionarily unrelated to chromosomal Dfrs. We report kinetic characterization of the known DfrB family members. Their kinetic constants are conserved and all are poorly inhibited by TMP, consistent with TMP resistance. We investigate their inhibition with known and novel bisubstrate inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK). Importantly, all are inhibited by the HPPK inhibitors, making these molecules dual-target inhibitors of two folate pathway enzymes that are strictly microbial.

Identifiers

PMID33214838
PMCPMC7667824
OpenAlexW3091297171

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.