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

2.50
HDL Handle:
http://hdl.handle.net/10033/78513
Title:
Genomewide identification of genetic determinants of antimicrobial drug resistance in Pseudomonas aeruginosa.
Authors:
Dötsch, Andreas; Becker, Tanja; Pommerenke, Claudia; Magnowska, Zofia; Jänsch, Lothar; Häussler, Susanne
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.
Affiliation:
Chronic Pseudomonas Infections Research Group, Helmholtz Center for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
Citation:
Genomewide identification of genetic determinants of antimicrobial drug resistance in Pseudomonas aeruginosa. 2009, 53 (6):2522-31 Antimicrob. Agents Chemother.
Journal:
Antimicrobial agents and chemotherapy
Issue Date:
Jun-2009
URI:
http://hdl.handle.net/10033/78513
DOI:
10.1128/AAC.00035-09
PubMed ID:
19332674
Type:
Article
Language:
en
ISSN:
1098-6596
Appears in Collections:
Publications of JRG Chronic Pseudomonas Diseases (CPI)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorDötsch, Andreas-
dc.contributor.authorBecker, Tanja-
dc.contributor.authorPommerenke, Claudia-
dc.contributor.authorMagnowska, Zofia-
dc.contributor.authorJänsch, Lothar-
dc.contributor.authorHäussler, Susanne-
dc.date.accessioned2009-08-25T14:04:44Z-
dc.date.available2009-08-25T14:04:44Z-
dc.date.issued2009-06-
dc.identifier.citationGenomewide identification of genetic determinants of antimicrobial drug resistance in Pseudomonas aeruginosa. 2009, 53 (6):2522-31 Antimicrob. Agents Chemother.en
dc.identifier.issn1098-6596-
dc.identifier.pmid19332674-
dc.identifier.doi10.1128/AAC.00035-09-
dc.identifier.urihttp://hdl.handle.net/10033/78513-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.subject.meshBacterial Outer Membrane Proteinsen
dc.subject.meshDNA Transposable Elementsen
dc.subject.meshDrug Resistance, Multiple, Bacterialen
dc.subject.meshMembrane Transport Proteinsen
dc.subject.meshMicrobial Sensitivity Testsen
dc.subject.meshMutationen
dc.subject.meshPseudomonas aeruginosaen
dc.titleGenomewide identification of genetic determinants of antimicrobial drug resistance in Pseudomonas aeruginosa.en
dc.typeArticleen
dc.contributor.departmentChronic Pseudomonas Infections Research Group, Helmholtz Center for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.en
dc.identifier.journalAntimicrobial agents and chemotherapyen

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