Evidence map›Paper›PMID 29431605›Full record

ArticleMicrobial genomics2018

Multifactorial chromosomal variants regulate polymyxin resistance in extensively drug-resistant Klebsiella pneumoniae.

Miranda E Pitt, Alysha G Elliott, Minh Duc Cao, Devika Ganesamoorthy, Ilias Karaiskos, Helen Giamarellou, Cely S Abboud, Mark A T Blaskovich, Matthew A Cooper, Lachlan J M Coin

Open access · goldAbstract read
In one paragraph

Article in Microbial genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 7% 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

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.

  1. Global prevalence of mutation in theFrontiers in microbiology · 2024
    Pooled it
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  11. Heteroresistance to Colistin in Clinical Isolates ofAntibiotics (Basel, Switzerland) · 2023
    Article
  12. Microbiology spectrum · 2023
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  13. Article
  14. Adaptive laboratory evolution ofFrontiers in microbiology · 2023
    Article
  15. Colistin Resistance Mechanisms in Human and VeterinaryAntibiotics (Basel, Switzerland) · 2022
    Article
  16. Characterization of Carbapenemase-ProducingAntibiotics (Basel, Switzerland) · 2022
    Article
  17. Article
  18. Article
  19. Colistin Resistance Mechanisms in HumanAntibiotics (Basel, Switzerland) · 2022
    Article
  20. 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

10 authors at 3 institutions in 3 countries.

Miranda E Pitt1​Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Alysha G Elliott1​Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Minh Duc Cao1​Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Devika Ganesamoorthy1​Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Ilias Karaiskos2​6th Department of Internal Medicine, Hygeia General Hospital, Athens, Greece.
Helen Giamarellou2​6th Department of Internal Medicine, Hygeia General Hospital, Athens, Greece.
Cely S Abboud3​Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil.
Mark A T Blaskovich1​Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Matthew A Cooper1​Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Lachlan J M Coin1​Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
University of Queensland · AUHygeia Hospital · GRInstituto Dante Pazzanese de Cardiologia · BR

Funding

Discovery of Polymyxin-based Antibacterial Agents Active Against Multi-Drug ResisR33AI098731 · NIAID · UNIVERSITY OF QUEENSLAND · PI COOPER, MATTHEW A, LASH, LAWRENCE H. · 2014 to 2016
$945k
Discovery of Polymyxin-based Antibacterial Agents Active Against Multi-Drug ResisR21AI098731 · NIAID · UNIVERSITY OF QUEENSLAND · PI COOPER, MATTHEW A, LASH, LAWRENCE H. · 2012 to 2013
$290k
NIAID NIH HHS R21 AI098731NIAID NIH HHS R33 AI098731Wellcome TrustWellcome Trust 104797/Z/14/Z
6 · The paper itself

Abstract

Extensively drug-resistant Klebsiella pneumoniae (XDR-KP) infections cause high mortality and are disseminating globally. Identifying the genetic basis underpinning resistance allows for rapid diagnosis and treatment. XDR isolates sourced from Greece and Brazil, including 19 polymyxin-resistant and five polymyxin-susceptible strains, were subjected to whole genome sequencing. Seventeen of the 19 polymyxin-resistant isolates harboured variations upstream or within mgrB. The most common mutation identified was an insertion at nucleotide position 75 in mgrB via an ISKpn26-like element in the ST258 lineage and ISKpn13 in one ST11 isolate. Three strains acquired an IS1 element upstream of mgrB and another strain had an ISKpn25 insertion at 133 bp. Other isolates had truncations (C28STOP, Q30STOP) or a missense mutation (D29E) affecting mgrB. Complementation assays revealed all mgrB perturbations contributed to resistance. Missense mutations in phoQ (T281M, G385C) were also found to facilitate resistance. Several variants in phoPQ co-segregating with the ISKpn26-like insertion were identified as potential partial suppressor mutations. Three ST258 samples were found to contain subpopulations with different resistance-conferring mutations, including the ISKpn26-like insertion colonizing with a novel mutation in pmrB (P158R), both confirmed via complementation assays. These findings highlight the broad spectrum of chromosomal modifications which can facilitate and regulate resistance against polymyxins in K. pneumoniae.

Indexed as

Anti-Bacterial AgentsBrazilChromosomes, BacterialColistinDNA, BacterialDrug Resistance, BacterialEscherichia coliGene Expression Regulation, BacterialGene LibraryGenes, BacterialGenetic VariationGreeceKlebsiella pneumoniaeMicrobial Sensitivity TestsMutationPolymyxinsAnti-Bacterial AgentsColistinDNA, BacterialPolymyxinsantibiotic resistancechromosomal variantsKlebsiella pneumoniaepolymyxin

Identifiers

PMID29431605
PMCPMC5885010
OpenAlexW2949638188

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.