Evidence map›Paper›PMID 25385117›Full record

ArticleAntimicrobial agents and chemotherapy2015

Genomic and transcriptomic analyses of colistin-resistant clinical isolates of Klebsiella pneumoniae reveal multiple pathways of resistance.

Meredith S Wright, Yo Suzuki, Marcus B Jones, Steven H Marshall, Susan D Rudin, David van Duin, Keith Kaye, Michael R Jacobs, Robert A Bonomo, Mark D Adams

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed, 2 pooled it
4.5field-weighted citation impact, top 4% 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

120 citing papers in PubMed, 2 syntheses or guidelines pooled it, 213 citations in OpenAlex.

  1. Global prevalence of mutation in theFrontiers in microbiology · 2024
    Pooled it
  2. Pooled it
  3. A posttranslational modification of fimbriae drives pathogenicity inProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. Carbapenem and colistin-resistantJAC-antimicrobial resistance · 2026
    Article
  8. Article
  9. Article
  10. Colistin Resistance in Bacteria: Current Updates on Mechanism of Action and Combating Strategies.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2026
    Review
  11. Antibiotic Resistance inAntibiotics (Basel, Switzerland) · 2026
    Review
  12. Review
  13. Article
  14. Article
  15. Emergence of concurrently transmissibleMicrobiology spectrum · 2025
    Article
  16. Review
  17. Article
  18. Review
  19. Colistin: Lights and Shadows of an Older Antibiotic.Molecules (Basel, Switzerland) · 2024
    Review
  20. Article

60 more citing papers are in PubMed but not listed here.

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

10 authors at 6 institutions in 1 country.

Meredith S WrightJ. Craig Venter Institute, La Jolla, California, USA.
Yo SuzukiJ. Craig Venter Institute, La Jolla, California, USA.
Marcus B JonesJ. Craig Venter Institute, La Jolla, California, USA.
Steven H MarshallResearch Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
Susan D RudinResearch Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA.
David van DuinDivision of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina.
Keith KayeDetroit Medical Center, Detroit, Michigan, USA.
Michael R JacobsDepartment of Pathology, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, USA.
Robert A BonomoResearch Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA Departments of Medicine, Pharmacology, Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio, USA Robert.Bonomo@va.gov madams@jcvi.org.
Mark D AdamsJ. Craig Venter Institute, La Jolla, California, USA Robert.Bonomo@va.gov madams@jcvi.org.
J. Craig Venter Institute · USLouis Stokes Cleveland VA Medical Center · USCase Western Reserve University · USDetroit Medical Center · USUnited States Department of Veterans Affairs · USUniversity of North Carolina at Chapel Hill · US

Funding

Antibacterial Resistance Leadership Group (ARLG)UM1AI104681 · NIAID · DUKE UNIVERSITY · PI Vance G. Fowler, Henry F HENRY CHAMBERS · 2013 to 2026
$180.8M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024989 · NCRR · CASE WESTERN RESERVE UNIVERSITY · PI DAVIS, PAMELA B · 2007 to 2011
$53.7M
Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
Understanding B-Lactam Resistance in Acinetobacter baumanniiR01AI072219 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI ROBERT A. BONOMO, Philip N. Rather · 2007 to 2026
$6.6M
Understanding ceftazidime resistance in SHV B-LactamasesR01AI063517 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI BONOMO, ROBERT A. · 2005 to 2023
$4.9M
Evolution of multidrug resistance in Acinetobacter baumanniiR01GM094403 · NIGMS · J. CRAIG VENTER INSTITUTE, INC. · PI ADAMS, MARK D · 2011 to 2014
$1.3M
The Continuing Challenge of Carbapenemases in K. pneumoniae: KPC-2 & NDM-1I01BX001974 · VA · LOUIS STOKES CLEVELAND VA MEDICAL CENTER · PI BONOMO, ROBERT A. · 2013 to 2024
–
BLRD VA I01 BX001974NCATS NIH HHS UL1 TR000439NCATS NIH HHS UL1TR000439NIAID NIH HHS HHSN272200900007CNIAID NIH HHS R01 AI063517NIAID NIH HHS R01AI063517NIAID NIH HHS R01 AI072219NIAID NIH HHS R01AI072219NIAID NIH HHS UM1 AI104681NIAID NIH HHS UM1AI104681NIGMS NIH HHS R01 GM094403NIGMS NIH HHS R01GM094403
6 · The paper itself

Abstract

The emergence of multidrug-resistant (MDR) Klebsiella pneumoniae has resulted in a more frequent reliance on treatment using colistin. However, resistance to colistin (Col(r)) is increasingly reported from clinical settings. The genetic mechanisms that lead to Col(r) in K. pneumoniae are not fully characterized. Using a combination of genome sequencing and transcriptional profiling by RNA sequencing (RNA-Seq) analysis, distinct genetic mechanisms were found among nine Col(r) clinical isolates. Col(r) was related to mutations in three different genes in K. pneumoniae strains, with distinct impacts on gene expression. Upregulation of the pmrH operon encoding 4-amino-4-deoxy-L-arabinose (Ara4N) modification of lipid A was found in all Col(r) strains. Alteration of the mgrB gene was observed in six strains. One strain had a mutation in phoQ. Common among these seven strains was elevated expression of phoPQ and unaltered expression of pmrCAB, which is involved in phosphoethanolamine addition to lipopolysaccharide (LPS). In two strains, separate mutations were found in a previously uncharacterized histidine kinase gene that is part of a two-component regulatory system (TCRS) now designated crrAB. In these strains, expression of pmrCAB, crrAB, and an adjacent glycosyltransferase gene, but not that of phoPQ, was elevated. Complementation with the wild-type allele restored colistin susceptibility in both strains. The crrAB genes are present in most K. pneumoniae genomes, but not in Escherichia coli. Additional upregulated genes in all strains include those involved in cation transport and maintenance of membrane integrity. Because the crrAB genes are present in only some strains, Col(r) mechanisms may be dependent on the genetic background.

Indexed as

Anti-Bacterial AgentsBacterial ProteinsColistinDrug Resistance, BacterialGene Expression Regulation, BacterialGenome, BacterialHumansKlebsiella pneumoniaeLipid AMutationOperonAnti-Bacterial AgentsBacterial ProteinsColistinLipid A

Identifiers

PMID25385117
PMCPMC4291396
OpenAlexW2064779430

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.