Transcriptome profiling of antimicrobial resistance in Pseudomonas aeruginosa

Ariane Khaledi, Monika Schniederjans, Sarah Pohl, Roman Rainer, Ulrich Bodenhofer, Boyang Xia, Frank Klawonn, Sebastian Bruchmann, Matthias Preusse, Denitsa Eckweiler, Andreas Dötsch, Susanne Häussler

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Emerging resistance to antimicrobials and the lack of new antibiotic drug candidates underscore the need for optimization of current diagnostics and therapies to diminish the evolution and spread of multidrug resistance. As the antibiotic resistance status of a bacterial pathogen is defined by its genome, resistance profiling by applying next-generation sequencing (NGS) technologies may in the future accomplish pathogen identification, prompt initiation of targeted individualized treatment, and the implementation of optimized infection control measures. In this study, qualitative RNA sequencing was used to identify key genetic determinants of antibiotic resistance in 135 clinical Pseudomonas aeruginosa isolates from diverse geographic and infection site origins. By applying transcriptome-wide association studies, adaptive variations associated with resistance to the antibiotic classes fluoroquinolones, aminoglycosides, and β-lactams were identified. Besides potential novel biomarkers with a direct correlation to resistance, global patterns of phenotype-associated gene expression and sequence variations were identified by predictive machine learning approaches. Our research serves to establish genotype-based molecular diagnostic tools for the identification of the current resistance profiles of bacterial pathogens and paves the way for faster diagnostics for more efficient, targeted treatment strategies to also mitigate the future potential for resistance evolution.

Original languageEnglish
Pages (from-to)4722-4733
Number of pages12
JournalAntimicrobial Agents and Chemotherapy
Volume60
Issue number8
DOIs
Publication statusPublished - Aug 2016

Keywords

  • Aminoglycosides/pharmacology
  • Anti-Bacterial Agents/pharmacology
  • Drug Resistance, Multiple, Bacterial/genetics
  • Fluoroquinolones/pharmacology
  • Gene Expression Profiling/methods
  • High-Throughput Nucleotide Sequencing/methods
  • Humans
  • Microbial Sensitivity Tests/methods
  • Pseudomonas Infections/drug therapy
  • Pseudomonas aeruginosa/drug effects
  • Transcriptome/genetics
  • beta-Lactams/pharmacology

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