Evidence map›Paper›PMID 22106224›Full record

ArticleAntimicrobial agents and chemotherapy2012

PmrB mutations promote polymyxin resistance of Pseudomonas aeruginosa isolated from colistin-treated cystic fibrosis patients.

Samuel M Moskowitz, Mark K Brannon, Nandini Dasgupta, Miyuki Pier, Nicole Sgambati, Amanda K Miller, Sara E Selgrade, Samuel I Miller, Miles Denton, Steven P Conway and 2 more

Open access · greenAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

129 citing papers in PubMed, 228 citations in OpenAlex.

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  14. Genome sequences of two highly colistin-resistantMicrobiology resource announcements · 2025
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  20. Article

69 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

12 authors at 4 institutions in 3 countries.

Samuel M MoskowitzDepartment of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts, USA. smoskowitz@partners.org
Mark K Brannon
Nandini Dasgupta
Miyuki Pier
Nicole Sgambati
Amanda K Miller
Sara E Selgrade
Samuel I Miller
Miles Denton
Steven P Conway
Helle K Johansen
Niels Høiby
University of Washington · USMassachusetts General Hospital · USLeeds Teaching Hospitals NHS Trust · GBRigshospitalet · DK

Funding

ROLE OF THE PHOP REGULON IN SALMONELLA VIRULENCER01AI030479 · NIAID · UNIVERSITY OF WASHINGTON · PI MILLER, SAMUEL I · 1991 to 2014
$5.3M
Polymyxin-resistant Pseudomonas in CF Lung InfectionR01AI067653 · NIAID · UNIVERSITY OF WASHINGTON · PI MOSKOWITZ, SAMUEL M · 2007 to 2010
$2.5M
Host-Pathogen Interactions in Cystic FibrosisK08HL067903 · NHLBI · UNIVERSITY OF WASHINGTON · PI MOSKOWITZ, SAMUEL M · 2001 to 2005
$628k
NHLBI NIH HHS K08 HL067903NHLBI NIH HHS K08HL067903NIAID NIH HHS R01 AI030479NIAID NIH HHS R01AI030479NIAID NIH HHS R01 AI067653NIAID NIH HHS R01AI067653
6 · The paper itself

Abstract

Pseudomonas aeruginosa can develop resistance to polymyxin and other cationic antimicrobial peptides. Previous work has shown that mutations in the PmrAB and PhoPQ regulatory systems can confer low to moderate levels of colistin (polymyxin E) resistance in laboratory strains and clinical isolates of this organism (MICs of 8 to 64 mg/liter). To explore the role of PmrAB in high-level clinical polymyxin resistance, P. aeruginosa isolates from chronically colistin-treated cystic fibrosis patients, most with colistin MICs of >512 mg/liter, were analyzed. These cystic fibrosis isolates contained probable gain-of-function pmrB alleles that conferred polymyxin resistance to strains with a wild-type or pmrAB deletion background. Double mutant pmrB alleles that contained mutations in both the periplasmic and dimerization-phosphotransferase domains markedly augmented polymyxin resistance. Expression of mutant pmrB alleles induced transcription from the promoter of the arnB operon and stimulated addition of 4-amino-l-arabinose to lipid A, consistent with the known role of this lipid A modification in polymyxin resistance. For some highly polymyxin-resistant clinical isolates, repeated passage without antibiotic selection pressure resulted in loss of resistance, suggesting that secondary suppressors occur at a relatively high frequency and account for the instability of this phenotype. These results indicate that pmrB gain-of-function mutations can contribute to high-level polymyxin resistance in clinical strains of P. aeruginosa.

Indexed as

MutationAnti-Bacterial AgentsBacterial ProteinsColistinCystic FibrosisDrug Resistance, BacterialGene Expression Regulation, BacterialHumansMicrobial Sensitivity TestsPolymyxinsPseudomonas aeruginosaTranscription FactorsAnti-Bacterial AgentsBacterial ProteinsColistinPmrB protein, bacteriaPolymyxinsTranscription Factors

Identifiers

PMID22106224
PMCPMC3264203
OpenAlexW2060967918

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.