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JAC Advance Access published online on January 22, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh074
© 2004 by The British Society for Antimicrobial Chemotherapy
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© 2004 The British Society for Antimicrobial Chemotherapy

Original article

Overexpression of the multidrug efflux pump SmeDEF impairs Stenotrophomonas maltophilia physiology

Ana Alonso 1 , Gracia Morales 1 , Ricardo Escalante 2 , Ester Campanario 1 , Leandro Sastre 2 , and Jose L. Martinez 1 *

1 Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma de Madrid, Cantoblanco, 28049-Madrid;
2 Instituto de Investigaciones Biomédicas, CSIC/UAM, C/ Arturo Duperier 4, 28029-Madrid, Spain

* Corresponding author. E-mail: jlmtnez{at}cnb.uam.es.

Received 13 October 2003 ; revised 13 November 2003 ; accepted 17 November 2003

Abstract

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.

Keywords: antibiotic resistance, S. maltophilia, MDR, bacterial fitness, metabolic profiling, virulence
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