Evidence map›Paper›PMID 23564252›Full record

ArticleGenome research2013

Genomic insights into the fate of colistin resistance and Acinetobacter baumannii during patient treatment.

Evan S Snitkin, Adrian M Zelazny, Jyoti Gupta, NISC Comparative Sequencing Program, Tara N Palmore, Patrick R Murray, Julia A Segre

Open access · bronzeAbstract read
In one paragraph

Article in Genome research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing 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

58 citing papers in PubMed, 102 citations in OpenAlex.

  1. A Clinically Silent Resistance Phenotype That PromotesbioRxiv : the preprint server for biology · 2026
    Article
  2. Resistance, heteroresistance, and fitness costs drive colistin treatment failure duringProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. 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
  4. Article
  5. Article
  6. Article
  7. Phenotypic and genetic heterogeneity ofMicrobial genomics · 2025
    Article
  8. Review
  9. Article
  10. ISmBio · 2024
    Article
  11. Reversions mask the contribution of adaptive evolution in microbiomes.bioRxiv : the preprint server for biology · 2024
    Article
  12. Polymyxins: recent advances and challenges.Frontiers in pharmacology · 2024
    Review
  13. Article
  14. Article
  15. Colistin Resistance inAntibiotics (Basel, Switzerland) · 2023
    Review
  16. Article
  17. Review
  18. Detecting bacterial adaptation within individual microbiomes.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022
    Review
  19. 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

7 authors at 5 institutions in 1 country.

Evan S SnitkinEpithelial Biology Section, GMBB, NHGRI, Bethesda, Maryland 20892, USA.
Adrian M Zelazny
Jyoti Gupta
NISC Comparative Sequencing Program
Tara N Palmore
Patrick R Murray
Julia A Segre
National Institutes of Health Clinical Center · USOffice of Extramural Research · USNational Human Genome Research Institute · USNational Institutes of Health · USOffice of the Director · US

Funding

Inter- and Intra-Species Comparative SequencingZIBHG000196 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI THOMAS, JAMES · 2009 to 2025
$177.6M
Microbial genomics of hospital-associated pathogensZIAHG200382 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI SEGRE, JULIA ANGELA · 2012 to 2025
$9.1M
Multidrug-resistant organism colonization in the Clinical CenterZIACL004041 · CLC · CLINICAL CENTER · PI PALMORE, TARA · 2014 to 2016
$0k
Studies of the Human Microbiome in Clinical Center PatientsZIACL004042 · CLC · CLINICAL CENTER · PI PALMORE, TARA · 2014 to 2021
$0k
Molecular and Virulence Traits of Bacteria & Fungi Causing Persistent InfectionsZIACL080013 · CLC · CLINICAL CENTER · PI ZELAZNY, ADRIAN MARCELO · 2009 to 2025
$0k
Intramural NIH HHS
6 · The paper itself

Abstract

Bacterial whole-genome sequencing (WGS) of human pathogens has provided unprecedented insights into the evolution of antibiotic resistance. Most studies have focused on identification of resistance mutations, leaving one to speculate on the fate of these mutants once the antibiotic selective pressure is removed. We performed WGS on longitudinal isolates of Acinetobacter baumannii from patients undergoing colistin treatment, and upon subsequent drug withdrawal. In each of the four patients, colistin resistance evolved via mutations at the pmr locus. Upon colistin withdrawal, an ancestral susceptible strain outcompeted resistant isolates in three of the four cases. In the final case, resistance was also lost, but by a compensatory inactivating mutation in the transcriptional regulator of the pmr locus. Notably, this inactivating mutation reduced the probability of reacquiring colistin resistance when subsequently challenged in vitro. On face value, these results supported an in vivo fitness cost preventing the evolution of stable colistin resistance. However, more careful analysis of WGS data identified genomic evidence for stable colistin resistance undetected by clinical microbiological assays. Transcriptional studies validated this genomic hypothesis, showing increased pmr expression of the initial isolate. Moreover, altering the environmental growth conditions of the clinical assay recapitulated the classification as colistin resistant. Additional targeted sequencing revealed that this isolate evolved undetected in a patient undergoing colistin treatment, and was then transmitted to other hospitalized patients, further demonstrating its stability in the absence of colistin. This study provides a unique window into mutational pathways taken in response to antibiotic pressure in vivo, and demonstrates the potential for genome sequence data to predict resistance phenotypes.

Indexed as

Genome, BacterialGenomicsAcinetobacter baumanniiAcinetobacter InfectionsAnti-Bacterial AgentsColistinDrug Resistance, BacterialGene Expression Regulation, BacterialGenes, BacterialGenetic FitnessHigh-Throughput Nucleotide SequencingHumansMicrobial Sensitivity TestsMutationPolymorphism, Single NucleotideAnti-Bacterial AgentsColistin

Identifiers

PMID23564252
PMCPMC3698508
OpenAlexW2152744936

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.