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Antimicrob Agents Chemother. 2016 Oct 21;60(11):6726-6734. doi: 10.1128/AAC.00724-16. Print 2016 Nov.

Molecular Epidemiology of Mutations in Antimicrobial Resistance Loci of Pseudomonas aeruginosa Isolates from Airways of Cystic Fibrosis Patients.

Author information

1
Clinical Research Group Molecular Pathology of Cystic Fibrosis, Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
2
Clinical Research Group Molecular Pathology of Cystic Fibrosis, Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany cramer.nina@mh-hannover.de tuemmler.burkhard@mh-hannover.de.
3
Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany.

Abstract

The chronic airway infections with Pseudomonas aeruginosa in people with cystic fibrosis (CF) are treated with aerosolized antibiotics, oral fluoroquinolones, and/or intravenous combination therapy with aminoglycosides and β-lactam antibiotics. An international strain collection of 361 P. aeruginosa isolates from 258 CF patients seen at 30 CF clinics was examined for mutations in 17 antimicrobial susceptibility and resistance loci that had been identified as hot spots of mutation by genome sequencing of serial isolates from a single CF clinic. Combinatorial amplicon sequencing of pooled PCR products identified 1,112 sequence variants that were not present in the genomes of representative strains of the 20 most common clones of the global P. aeruginosa population. A high frequency of singular coding variants was seen in spuE, mexA, gyrA, rpoB, fusA1, mexZ, mexY, oprD, ampD, parR, parS, and envZ (amgS), reflecting the pressure upon P. aeruginosa in lungs of CF patients to generate novel protein variants. The proportion of nonneutral amino acid exchanges was high. Of the 17 loci, mexA, mexZ, and pagL were most frequently affected by independent stop mutations. Private and de novo mutations seem to play a pivotal role in the response of P. aeruginosa populations to the antimicrobial load and the individual CF host.

PMID:
27572404
PMCID:
PMC5075079
DOI:
10.1128/AAC.00724-16
[Indexed for MEDLINE]
Free PMC Article

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