title: Transcriptome Profiling of Antimicrobial Resistance in Pseudomonas aeruginosa.
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.
authors.affiliation: Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany Institute for Molecular Bacteriology, TWINCORE GmbH, Centre for Clinical and Experimental Infection Research, Hanover, Germany.
authors.forename: Ariane
authors.initials: A
authors.lastname: Khaledi
authors.affiliation: Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany Institute for Molecular Bacteriology, TWINCORE GmbH, Centre for Clinical and Experimental Infection Research, Hanover, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Schniederjans
authors.affiliation: Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany Institute for Molecular Bacteriology, TWINCORE GmbH, Centre for Clinical and Experimental Infection Research, Hanover, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Pohl
authors.affiliation: Institute of Bioinformatics, Johannes Kepler University, Linz, Austria.
authors.forename: Roman
authors.initials: R
authors.lastname: Rainer
authors.affiliation: Institute of Bioinformatics, Johannes Kepler University, Linz, Austria.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bodenhofer
authors.affiliation: Institute of Bioinformatics, Johannes Kepler University, Linz, Austria.
authors.forename: Boyang
authors.initials: B
authors.lastname: Xia
authors.affiliation: Research Group Bioinformatics and Statistics, Helmholtz Centre for Infection Research, Braunschweig, Germany Department of Computer Science, Ostfalia University of Applied Sciences, Wolfenbuettel, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Klawonn
authors.affiliation: Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany Institute for Molecular Bacteriology, TWINCORE GmbH, Centre for Clinical and Experimental Infection Research, Hanover, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bruchmann
authors.affiliation: Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany Institute for Molecular Bacteriology, TWINCORE GmbH, Centre for Clinical and Experimental Infection Research, Hanover, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusse
authors.affiliation: Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany Institute for Molecular Bacteriology, TWINCORE GmbH, Centre for Clinical and Experimental Infection Research, Hanover, Germany.
authors.forename: Denitsa
authors.initials: D
authors.lastname: Eckweiler
authors.affiliation: Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany Institute for Molecular Bacteriology, TWINCORE GmbH, Centre for Clinical and Experimental Infection Research, Hanover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Dötsch
authors.affiliation: Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany Institute for Molecular Bacteriology, TWINCORE GmbH, Centre for Clinical and Experimental Infection Research, Hanover, Germany susanne.haeussler@helmholtz-hzi.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Häussler
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D024841:Fluoroquinolones / Q000494:pharmacology; D020869:Gene Expression Profiling / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics*; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D047090:beta-Lactams