Molecular Epidemiology of Mutations in Antimicrobial Resistance Loci of Pseudomonas aeruginosa Isolates from Airways of Cystic Fibrosis Patients
| Autor: | Lutz Wiehlmann, Samira Mielke, Burkhard Tümmler, Jens Klockgether, Marie Dorda, Sebastian Fischer, Leonie Greipel, Nina Cramer |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Protein Conformation
alpha-Helical 0301 basic medicine Cystic Fibrosis medicine.drug_class Respiratory System 030106 microbiology Population Antibiotics Microbial Sensitivity Tests Biology medicine.disease_cause Cystic fibrosis Epidemiology and Surveillance Microbiology 03 medical and health sciences Antibiotic resistance Bacterial Proteins Drug Resistance Multiple Bacterial medicine Humans Protein Interaction Domains and Motifs Pseudomonas Infections Pharmacology (medical) Amino Acid Sequence education Pharmacology Molecular Epidemiology education.field_of_study Molecular epidemiology Pseudomonas aeruginosa High-Throughput Nucleotide Sequencing Antimicrobial medicine.disease rpoB Anti-Bacterial Agents Clone Cells Infectious Diseases Amino Acid Substitution Genes Bacterial Genetic Loci Mutation Sequence Alignment Genome Bacterial |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 60:6726-6734 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.00724-16 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|