Genomewide identification of genetic determinants of antimicrobial drug resistance in Pseudomonas aeruginosa

Andreas Dötsch, Tanja Becker, Claudia Pommerenke, Zofia Magnowska, Lothar Jänsch, Susanne Häussler

Abstract

The emergence of antimicrobial drug resistance is of enormous public concern due to the increased risk of delayed treatment of infections, the increased length of hospital stays, the substantial increase in the cost of care, and the high risk of fatal outcomes. A prerequisite for the development of effective therapy alternatives is a detailed understanding of the diversity of bacterial mechanisms that underlie drug resistance, especially for problematic gram-negative bacteria such as Pseudomonas aeruginosa. This pathogen has impressive chromosomally encoded mechanisms of intrinsic resistance, as well as the potential to mutate, gaining resistance to current antibiotics. In this study we have screened the comprehensive nonredundant Harvard PA14 library for P. aeruginosa mutants that exhibited either increased or decreased resistance against 19 antibiotics commonly used in the clinic. This approach identified several genes whose inactivation sensitized the bacteria to a broad spectrum of different antimicrobials and uncovered novel genetic determinants of resistance to various classes of antibiotics. Knowledge of the enhancement of bacterial susceptibility to existing antibiotics and of novel resistance markers or modifiers of resistance expression may lay the foundation for effective therapy alternatives and will be the basis for the development of new strategies in the control of problematic multiresistant gram-negative bacteria.

Original languageEnglish
JournalAntimicrobial Agents and Chemotherapy
Volume53
Issue number6
Pages (from-to)2522-31
Number of pages10
ISSN0066-4804
DOIs
Publication statusPublished - Jun 2009
Externally publishedYes

Keywords

  • Bacterial Outer Membrane Proteins/genetics
  • DNA Transposable Elements
  • Drug Resistance, Multiple, Bacterial/genetics
  • Membrane Transport Proteins/genetics
  • Microbial Sensitivity Tests
  • Mutation
  • Pseudomonas aeruginosa/drug effects

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