Evidence map›Paper›PMID 31629958›Full record

ArticleJournal of proteomics2020

The anti-MRSA compound 3-O-alpha-L-(2″,3″-di-p-coumaroyl)rhamnoside (KCR) inhibits protein synthesis in Staphylococcus aureus.

Nicholas J Carruthers, Paul M Stemmer, Joe Media, Ken Swartz, Xiaojuan Wang, Nicholas Aube, Mark T Hamann, Frederick Valeriote, Jiajiu Shaw

Abstract read
In one paragraph

Article in Journal of proteomics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

9 authors.

Nicholas J CarruthersInstitute of Environmental Health Sciences, Wayne State University, Detroit, MI 48201, USA; Wayne State University, Institute of Environmental Health Sciences, 2309 Scott Hall, 540 E Canfield Ave, Detroit, MI 48202, United States of America. Electronic address: carruthers@wayne.edu.
Paul M StemmerInstitute of Environmental Health Sciences, Wayne State University, Detroit, MI 48201, USA. Electronic address: pmstemmer@wayne.edu.
Joe MediaDepartment of Internal Medicine, Henry Ford Hospital, Detroit, MI 48201, USA. Electronic address: JMEDIA1@hfhs.org.
Ken SwartzDepartment of Internal Medicine, Henry Ford Hospital, Detroit, MI 48201, USA. Electronic address: KSWARTZ1@hfhs.org.
Xiaojuan WangDepartment of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.
Nicholas AubeDepartment of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address: aube@musc.edu.
Mark T HamannDepartment of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address: hamannm@musc.edu.
Frederick ValerioteDepartment of Internal Medicine, Henry Ford Hospital, Detroit, MI 48201, USA. Electronic address: FVALERI1@hfhs.org.
Jiajiu ShawHenry Ford Health System, Detroit, MI, USA; 21st Century Therapeutics, Detroit, MI 48201, USA.

Funding

Tumor Biology and Microenvironment (Program 1)P30CA022453 · NCI · WAYNE STATE UNIVERSITY · PI PAUL M STEMMER · 1985 to 2026
$68.4M
Pilot Project ProgramP30ES020957 · NIEHS · WAYNE STATE UNIVERSITY · PI RUNGE-MORRIS, MELISSA A · 2014 to 2021
$10.1M
Natural Product HCV Drugs from Rare Plant-Microbe InteractionsR01AT007318 · NCCIH · UNIVERSITY OF MISSISSIPPI · PI HAMANN, MARK T · 2012 to 2016
$1.6M
Orbitrap Velos with ETD for Wayne State ProteomicsS10OD010700 · OD · WAYNE STATE UNIVERSITY · PI STEMMER, PAUL M · 2012 to 2012
$575k
Novel Compounds from Sycamore Leaves for the Treatment of MRSAR43AT008202 · NCCIH · 21ST CENTURY THERAPEUTICS, INC. · PI CHEN, BEN D. · 2015 to 2016
$309k
NCCIH NIH HHS R01 AT007318NCCIH NIH HHS R43 AT008202NCI NIH HHS P30 CA022453NIEHS NIH HHS P30 ES020957NIH HHS S10 OD010700
6 · The paper itself

Abstract

Methicillin-resistant S aureus (MRSA) contributes to patient mortality and extended hospital stays. 3-O-alpha-L-(2″,3″-di-p-coumaroyl)rhamnoside (KCR) is a natural product antibiotic that is effective against MRSA but has no known mechanism of action (MOA). We used proteomics to identify the MOA for KCR. Methicillin sensitive S aureus and a mixture of four KCR stereoisomers were tested. A time-kill assay was used to choose a 4 h treatment using KCR at 5× its MIC for proteomic analysis. S aureus was treated in triplicate with KCR, oxacillin or vehicle and quantitative proteomic analysis was carried out using isobaric tags and mass spectrometry. 1190 proteins were identified and 552 were affected by KCR (q < 0.01). Ontology analysis identified 6 distinct translation-related categories that were affected by KCR (PIANO, 10% false-discovery rate) including structural constituent of ribosome, translation, rRNA binding, tRNA binding, tRNA processing and aminoacyl-tRNA ligase activity. Median fold changes (KCR vs Control) for small and large ribosomal components were 1.46 and 1.43 respectively. KCR inhibited the production of luciferase protein in an in vitro assay (IC50 39.6 μg/ml). Upregulation of translation-related proteins in response to KCR indicates that KCR acts to disrupt S aureus protein synthesis. This was confirmed with an in vitro transcription/translation assay. SIGNIFICANCE: Methicillin-resistant S aureus (MRSA) contributes to patient mortality and extended hospital stays. 3-O-alpha-L-(2″,3″-di-p-coumaroyl)rhamnoside (KCR) is a natural product antibiotic that is effective against MRSA but has no known mechanism of action (MOA). Using proteomic analysis we determined that KCR acts by inhibiting protein synthesis. KCR is an exciting novel antibiotic and this work represents an important step in its development towards clinical use.

Indexed as

Protein BiosynthesisAnti-Bacterial AgentsBacterial ProteinsHumansKaempferolsMethicillin-Resistant Staphylococcus aureusMicrobial Sensitivity TestsProtein Synthesis InhibitorsProteomicsRhamnoseStaphylococcal InfectionsAnti-Bacterial AgentsBacterial Proteinskaempferol-3-O-alpha-L-(2',3'-di-p-coumaroyl)rhamnosideKaempferolsProtein Synthesis InhibitorsRhamnose3-O-alpha-L-(2″,3″-di-p-coumaroyl)rhamnosideKCRMechanism of actionMethicillin-resistantProteomicsStaphylococcus aureus

Identifiers

PMID31629958
PMCPMC7014561

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Registered trials

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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.