Evidence map›Paper›PMID 29728636›Full record

ArticleScientific reports2018

Propyl-5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC): a new bacteriostatic agent against methicillin-resistant Staphylococcus aureus.

Tatiana Johnston, Daria Van Tyne, Roy F Chen, Nicolas L Fawzi, Bumsup Kwon, Michael J Kelso, Michael S Gilmore, Eleftherios Mylonakis

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 38% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Thermodynamic vs. Kinetic Control in Synthesis ofMolecules (Basel, Switzerland) · 2022
    Article
  2. Review
  3. Review
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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

8 authors at 3 institutions in 2 countries.

Tatiana JohnstonDepartment of Infectious Disease, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, USA.
Daria Van TyneDepartment of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
Roy F ChenDepartment of Infectious Disease, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, USA.
Nicolas L FawziDepartment of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, Providence, Rhode Island, USA.ORCID 0000-0001-5483-0577
Bumsup KwonDepartment of Neurology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA.
Michael J KelsoSchool of Chemistry and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2522, Australia.ORCID 0000-0001-7809-6637
Michael S GilmoreDepartment of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.
Eleftherios MylonakisDepartment of Infectious Disease, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, USA. emylonakis@lifespan.org.
Brown University · USMassachusetts Eye and Ear Infirmary · USUniversity of Wollongong · AU

Funding

Technical Mother Machine CoreP01AI083214 · NIAID · SCHEPENS EYE RESEARCH INSTITUTE · PI Michael S Gilmore · 2009 to 2026
$39.4M
Bacterial Evasion of Innate Defenses at the Ocular SurfaceR00EY028222 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI VAN TYNE, DARIA N · 2018 to 2020
$728k
Bacterial Evasion of Innate Defenses at the Ocular SurfaceK99EY028222 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI VAN TYNE, DARIA N · 2017 to 2017
$95k
NEI NIH HHS K99 EY028222NEI NIH HHS R00 EY028222NIAID NIH HHS P01 AI083214
6 · The paper itself

Abstract

The emergence of Staphylococcus aureus strains resistant to 'last resort' antibiotics compels the development of new antimicrobials against this important human pathogen. We found that propyl 5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC) shows bacteriostatic activity against S. aureus (MIC = 4 μg/ml) and rescues Caenorhabditis elegans from S. aureus infection. Whole-genome sequencing of S. aureus mutants resistant to the compound, along with screening of a S. aureus promoter-lux reporter array, were used to explore possible mechanisms of action. All mutants resistant to HMPC acquired missense mutations at distinct codon positions in the global transcriptional regulator mgrA, followed by secondary mutations in the phosphatidylglycerol lysyltransferase fmtC/mprF. The S. aureus promoter-lux array treated with HMPC displayed a luminescence profile that was unique but showed similarity to DNA-damaging agents and/or DNA replication inhibitors. Overall, HMPC is a new anti-staphylococcal compound that appears to act via an unknown mechanism linked to the global transcriptional regulator MgrA.

Indexed as

Anti-Bacterial AgentsBacterial ProteinsCell Line, TumorDNA-Binding ProteinsDose-Response Relationship, DrugGenome, BacterialHumansMethicillin-Resistant Staphylococcus aureusMicrobial Sensitivity TestsModels, MolecularMolecular ConformationMolecular StructureMutationStructure-Activity RelationshipWhole Genome SequencingAnti-Bacterial AgentsBacterial ProteinsDNA-Binding Proteins

Identifiers

PMID29728636
PMCPMC5935714
OpenAlexW2807191804

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.