Overexpression of the multidrug efflux pump SmeDEF impairs Stenotrophomonas maltophilia physiology

Objectives: The use of antibiotics for the treatment of infectious diseases has led to important changes in the structure of pathogenic bacterial populations. However, these changes could be buffered if the expression of antibiotic resistance genes were to lead to the counter-selection of antibiotic...

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Veröffentlicht in:Journal of antimicrobial chemotherapy 2004-03, Vol.53 (3), p.432-434
Hauptverfasser: Alonso, Ana, Morales, Gracia, Escalante, Ricardo, Campanario, Ester, Sastre, Leandro, Martinez, Jose L.
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container_end_page 434
container_issue 3
container_start_page 432
container_title Journal of antimicrobial chemotherapy
container_volume 53
creator Alonso, Ana
Morales, Gracia
Escalante, Ricardo
Campanario, Ester
Sastre, Leandro
Martinez, Jose L.
description Objectives: The use of antibiotics for the treatment of infectious diseases has led to important changes in the structure of pathogenic bacterial populations. However, these changes could be buffered if the expression of antibiotic resistance genes were to lead to the counter-selection of antibiotic-resistant strains in antibiotic-free environments. To test the effect of antibiotic resistance on bacterial fitness, we analysed the effect of the overproduction of the multidrug efflux pump SmeDEF on the physiology of Stenotrophomonas maltophilia. SmeDEF confers resistance to antibiotics belonging to different structural families, and its overexpression is associated with an antibiotic resistance phenotype in clinical isolates of S. maltophilia. Results: Two S. maltophilia isogenic strains were analysed: the wild-type strain D457 and strain D457R, which is a SmeDEF overproducer. In co-culture experiments, under non-selective pressure the wild-type strain displaced the mutant strain D457R. Metabolic profiling showed that SmeDEF overproduction leads to several changes in S. maltophilia metabolism. Using a Dictyostelium discoideum model of bacterial virulence, we found overexpression of SmeDEF to be associated with a reduction in S. maltophilia virulence. Conclusions: Together, these data indicate that overexpression of the multidrug efflux pump SmeDEF causes a metabolic burden for S. maltophilia.
doi_str_mv 10.1093/jac/dkh074
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However, these changes could be buffered if the expression of antibiotic resistance genes were to lead to the counter-selection of antibiotic-resistant strains in antibiotic-free environments. To test the effect of antibiotic resistance on bacterial fitness, we analysed the effect of the overproduction of the multidrug efflux pump SmeDEF on the physiology of Stenotrophomonas maltophilia. SmeDEF confers resistance to antibiotics belonging to different structural families, and its overexpression is associated with an antibiotic resistance phenotype in clinical isolates of S. maltophilia. Results: Two S. maltophilia isogenic strains were analysed: the wild-type strain D457 and strain D457R, which is a SmeDEF overproducer. In co-culture experiments, under non-selective pressure the wild-type strain displaced the mutant strain D457R. Metabolic profiling showed that SmeDEF overproduction leads to several changes in S. maltophilia metabolism. Using a Dictyostelium discoideum model of bacterial virulence, we found overexpression of SmeDEF to be associated with a reduction in S. maltophilia virulence. Conclusions: Together, these data indicate that overexpression of the multidrug efflux pump SmeDEF causes a metabolic burden for S. maltophilia.</description><identifier>ISSN: 0305-7453</identifier><identifier>ISSN: 1460-2091</identifier><identifier>EISSN: 1460-2091</identifier><identifier>DOI: 10.1093/jac/dkh074</identifier><identifier>PMID: 14739147</identifier><identifier>CODEN: JACHDX</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Animals ; antibiotic resistance ; Antibiotics. Antiinfectious agents. 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SmeDEF confers resistance to antibiotics belonging to different structural families, and its overexpression is associated with an antibiotic resistance phenotype in clinical isolates of S. maltophilia. Results: Two S. maltophilia isogenic strains were analysed: the wild-type strain D457 and strain D457R, which is a SmeDEF overproducer. In co-culture experiments, under non-selective pressure the wild-type strain displaced the mutant strain D457R. Metabolic profiling showed that SmeDEF overproduction leads to several changes in S. maltophilia metabolism. Using a Dictyostelium discoideum model of bacterial virulence, we found overexpression of SmeDEF to be associated with a reduction in S. maltophilia virulence. Conclusions: Together, these data indicate that overexpression of the multidrug efflux pump SmeDEF causes a metabolic burden for S. maltophilia.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>14739147</pmid><doi>10.1093/jac/dkh074</doi><tpages>3</tpages><oa>free_for_read</oa></addata></record>
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source Oxford University Press Journals All Titles (1996-Current); MEDLINE; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry
subjects Animals
antibiotic resistance
Antibiotics. Antiinfectious agents. Antiparasitic agents
bacterial fitness
Bacterial Proteins - biosynthesis
Bacterial Proteins - genetics
Biological and medical sciences
Culture Media
Dictyostelium - genetics
Dictyostelium - growth & development
Dictyostelium discoideum
Drug Resistance, Multiple, Bacterial - genetics
MDR
Medical sciences
Membrane Transport Proteins - biosynthesis
Membrane Transport Proteins - genetics
metabolic profiling
Pharmacology. Drug treatments
Phenotype
S. maltophilia
Stenotrophomonas maltophilia
Stenotrophomonas maltophilia - genetics
Stenotrophomonas maltophilia - growth & development
Stenotrophomonas maltophilia - physiology
virulence
Virulence - physiology
title Overexpression of the multidrug efflux pump SmeDEF impairs Stenotrophomonas maltophilia physiology
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