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Antimicrobial Agents and Chemotherapy, June 2009, p. 2522-2531, Vol. 53, No. 6
0066-4804/09/$08.00+0     doi:10.1128/AAC.00035-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Genomewide Identification of Genetic Determinants of Antimicrobial Drug Resistance in Pseudomonas aeruginosa{triangledown}

Andreas Dötsch,1 Tanja Becker,1 Claudia Pommerenke,1 Zofia Magnowska,2 Lothar Jänsch,2 and Susanne Häussler1,3*

Chronic Pseudomonas Infection Research Group,1 Proteomics Group, Helmholtz Center for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig,2 TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture of the Medical School Hannover and Helmholtz Center for Infection Research, Feodor-Lynen-Str. 7, D-30625 Hannover, Germany3

Received 9 January 2009/ Returned for modification 5 February 2009/ Accepted 21 March 2009

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.

* Corresponding author. Mailing address: Young Investigator Research Group, Chronic Pseudomonas Infections, Helmholtz Center for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany. Phone: 49-531-6181, ext. 3150. Fax: 49-531-6181, ext. 3099. E-mail: susanne.haeussler{at}helmholtz-hzi.de

{triangledown} Published ahead of print on 30 March 2009.

Antimicrobial Agents and Chemotherapy, June 2009, p. 2522-2531, Vol. 53, No. 6
0066-4804/09/$08.00+0     doi:10.1128/AAC.00035-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lister, P. D., Wolter, D. J., Hanson, N. D. (2009). Antibacterial-Resistant Pseudomonas aeruginosa: Clinical Impact and Complex Regulation of Chromosomally Encoded Resistance Mechanisms. Clin. Microbiol. Rev. 22: 582-610 [Abstract] [Full Text]  


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