Evidence map›Paper›PMID 25222597›Full record

ArticleACS chemical biology2014

Novel imidazoline antimicrobial scaffold that inhibits DNA replication with activity against mycobacteria and drug resistant Gram-positive cocci.

Kendra K Harris, Allison Fay, Han-Guang Yan, Pratima Kunwar, Nicholas D Socci, Narender Pottabathini, Ramakrishna R Juventhala, Hakim Djaballah, Michael S Glickman

Open access · greenAbstract read
In one paragraph

Article in ACS chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 27% 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

6 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Insights onFrontiers in microbiology · 2018
    Article
  4. Article
  5. Review
  6. 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 at 3 institutions in 2 countries.

Kendra K HarrisProgram in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences , New York, New York 10021, United States.
Allison Fay
Han-Guang Yan
Pratima Kunwar
Nicholas D Socci
Narender Pottabathini
Ramakrishna R Juventhala
Hakim Djaballah
Michael S Glickman
Cornell University · USVirchow BioTech (India) · INUniversity of Washington · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Weill Cornell/Rockefeller/Sloan-Kettering MST ProgramT32GM007739 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HSU, KATHARINE C · 1985 to 2023
$51.1M
Vanderbilt-Emory-Cornell-Duke Consortium for Global Health Fellows (VECDor)R25TW009337 · FIC · VANDERBILT UNIVERSITY MEDICAL CENTER · PI HEIMBURGER, DOUGLAS CORBETT, VERMUND, STEN H. · 2012 to 2016
$6.3M
IMMUNOLOGY RESEARCH TRAININGT32CA009149 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI RUDENSKY, ALEXANDER Y · 1985 to 2022
$4.0M
FIC NIH HHS R25 TW009337FIC NIH HHS T32TW009337NCI NIH HHS P30 CA008748NCI NIH HHS P30CA008748NCI NIH HHS T32 CA009149NCI NIH HHS T32CA009149NIGMS NIH HHS T32 GM007739NIGMS NIH HHS T32GM007739
6 · The paper itself

Abstract

Bacterial antimicrobial resistance is an escalating public health threat, yet the current antimicrobial pipeline remains alarmingly depleted, making the development of new antimicrobials an urgent need. Here, we identify a novel, potent, imidazoline antimicrobial compound, SKI-356313, with bactericidal activity against Mycobacterium tuberculosis and Gram-positive cocci, including vancomycin-resistant Enterococcus faecium (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). SKI-356313 is active in murine models of Streptococcus pneumoniae and MRSA infection and is potently bactericidal for both replicating and nonreplicating M. tuberculosis. Using a combination of genetics, whole genome sequencing, and a novel target ID approach using real time imaging of core macromolecular biosynthesis, we show that SKI-356313 inhibits DNA replication and displaces the replisome from the bacterial nucleoid. These results identify a new antimicrobial scaffold with a novel mechanism of action and potential therapeutic utility against nonreplicating M. tuberculosis and antibiotic resistant Gram-positive cocci.

Indexed as

AnimalsAnti-Bacterial AgentsDNA ReplicationGram-Positive CocciImidazolinesMiceMutationMycobacteriumStructure-Activity RelationshipAnti-Bacterial AgentsImidazolines

Identifiers

PMID25222597
PMCPMC4245167
OpenAlexW2335627788

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.