Evidence map›Paper›PMID 31374222›Full record

ArticleThe Journal of infection2019

Multifaceted mechanisms of colistin resistance revealed by genomic analysis of multidrug-resistant Klebsiella pneumoniae isolates from individual patients before and after colistin treatment.

Yan Zhu, Irene Galani, Ilias Karaiskos, Jing Lu, Su Mon Aye, Jiayuan Huang, Heidi H Yu, Tony Velkov, Helen Giamarellou, Jian Li

Abstract read
In one paragraph

Article in The Journal of infection, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 20% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Global prevalence of mutation in theFrontiers in microbiology · 2024
    Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Insertion sequences inFrontiers in microbiology · 2025
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Prevalence of Mutated Colistin-ResistantTropical medicine and infectious disease · 2022
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Risk Factors for and Mechanisms ofOpen forum infectious diseases · 2021
    Article
  19. A Bibliometric Meta-Analysis of Colistin Resistance inDiseases (Basel, Switzerland) · 2021
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

Yan ZhuMonash Biomedicine Discovery Institute, Infection and Immunity Program and Department of Microbiology, Monash University, Melbourne 3800, Australia. Electronic address: yan.zhu@monash.edu.
Irene GalaniFourth Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: egalani@med.uoa.gr.
Ilias KaraiskosFirst Department of Internal Medicine - Infectious Diseases, Hygeia General Hospital, Athens, Greece. Electronic address: ikaraiskos@hygeia.gr.
Jing LuMonash Biomedicine Discovery Institute, Infection and Immunity Program and Department of Microbiology, Monash University, Melbourne 3800, Australia. Electronic address: jing.lu2@monash.edu.
Su Mon AyeMonash Biomedicine Discovery Institute, Infection and Immunity Program and Department of Microbiology, Monash University, Melbourne 3800, Australia. Electronic address: su.aye@monash.edu.
Jiayuan HuangMonash Biomedicine Discovery Institute, Infection and Immunity Program and Department of Microbiology, Monash University, Melbourne 3800, Australia. Electronic address: jiayuan.huang@monash.edu.
Heidi H YuMonash Biomedicine Discovery Institute, Infection and Immunity Program and Department of Microbiology, Monash University, Melbourne 3800, Australia. Electronic address: heidi.yu@monash.edu.
Tony VelkovDepartment of Pharmacology and Therapeutics, University of Melbourne, Melbourne 3010, Australia. Electronic address: tony.velkov@unimelb.edu.au.
Helen GiamarellouFirst Department of Internal Medicine - Infectious Diseases, Hygeia General Hospital, Athens, Greece. Electronic address: e.giamarellou@hygeia.gr.
Jian LiMonash Biomedicine Discovery Institute, Infection and Immunity Program and Department of Microbiology, Monash University, Melbourne 3800, Australia. Electronic address: jian.li@monash.edu.
Monash University · AUHygeia Hospital · GRNational and Kapodistrian University of Athens · GRUniversity of Melbourne · AU

Funding

Targeting the Urgent Need for New Antibiotics against Gram-negative ‘Superbugs’R01AI132154 · NIAID · MONASH UNIVERSITY · PI LI, JIAN, VELKOV, TONY · 2017 to 2021
$4.3M
NIAID NIH HHS R01 AI132154
6 · The paper itself

Abstract

objectivesPolymyxins (i.e., polymyxin B and colistin) are used as a last-line therapy to combat multidrug-resistant (MDR) Klebsiella pneumoniae. Worryingly, polymyxin resistance in K. pneumoniae is increasingly reported worldwide. This study identified the genetic variations responsible for high-level colistin resistance in MDR K. pneumoniae clinical isolates.

methodsSixteen MDR K. pneumoniae isolates were obtained from stool samples of 8 patients before and after colistin treatment. Their genomes were sequenced on Illumina MiSeq to determine genetic variations.

resultsFifteen of 16 isolates harboured ISKpn26-like element insertion at nucleotide position 75 of mgrB, abolishing its negative regulation on phoPQ; while colistin-susceptible ATH7 contained intact mgrB and phoQ. Interestingly, each of the 7 mgrB-disrupted, colistin-susceptible isolates contained a nonsynonymous substitution in PhoQ (G39S, L239P, N253T or V446G), potentially impairing its function and intergenically suppressing the effect caused by mgrB inactivation. Additionally, three of the 7 corresponding mgrB-disrupted, colistin-resistant isolates harboured a secondary nonsynonymous substitution in PhoQ (N253P, D438H or T439P).

conclusionsThis is the first report of phoQ mutations in mgrB-disrupted, colistin-susceptible K. pneumoniae clinical isolates. We also discovered multiple phoQ mutations in mgrB-disrupted, colistin-resistant strains. Our findings highlight the multifaceted molecular mechanisms of colistin resistance in K. pneumoniae.

Indexed as

Anti-Bacterial AgentsBacterial ProteinsColistinDNA Transposable ElementsDrug Resistance, Multiple, BacterialHumansKlebsiella InfectionsKlebsiella pneumoniaeMembrane ProteinsMicrobial Sensitivity TestsAnti-Bacterial AgentsBacterial ProteinsColistinDNA Transposable ElementsMembrane ProteinsPhoQ protein, BacteriaColistinGenomicsKlebsiella pneumoniaemgrBphoQ

Identifiers

PMID31374222
PMCPMC7264071
OpenAlexW2967854104

What OpenQuestion holds

Textmetadata
LicenceTDM
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.