title: Molecular Epidemiology of Mutations in Antimicrobial Resistance Loci of Pseudomonas aeruginosa Isolates from Airways of Cystic Fibrosis Patients.
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.
authors: Clinical Research Group Molecular Pathology of Cystic Fibrosis, Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
authors: Leonie
authors: L
authors: Greipel
authors: Clinical Research Group Molecular Pathology of Cystic Fibrosis, Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
authors: Sebastian
authors: S
authors: Fischer
authors: Clinical Research Group Molecular Pathology of Cystic Fibrosis, Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
authors: Jens
authors: J
authors: Klockgether
authors: Clinical Research Group Molecular Pathology of Cystic Fibrosis, Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
authors: Marie
authors: M
authors: Dorda
authors: Clinical Research Group Molecular Pathology of Cystic Fibrosis, Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
authors: Samira
authors: S
authors: Mielke
authors: Clinical Research Group Molecular Pathology of Cystic Fibrosis, Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.
authors: Lutz
authors: L
authors: Wiehlmann
authors: 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.
authors: Nina
authors: N
authors: Cramer
authors: 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.|Biomedical Research in Endstage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany.
authors: Burkhard
authors: B
authors: Tümmler
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002999:Clone Cells; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005798:Genes, Bacterial; D056426:Genetic Loci; D016680:Genome, Bacterial; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008826:Microbial Sensitivity Tests; D017720:Molecular Epidemiology; D009154:Mutation; D000072756:Protein Conformation, alpha-Helical; D054730:Protein Interaction Domains and Motifs; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D016415:Sequence Alignment
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C402792:MexZ protein, Pseudomonas aeruginosa