title: Overexpression of the multidrug efflux pump SmeDEF impairs Stenotrophomonas maltophilia physiology.
abstract: OBJECTIVE
  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.
authors.affiliation: Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma de Madrid, Cantoblanco, 28049-Madrid.
authors.forename: Ana
authors.initials: A
authors.lastname: Alonso
authors.forename: Gracia
authors.initials: G
authors.lastname: Morales
authors.forename: Ricardo
authors.initials: R
authors.lastname: Escalante
authors.forename: Ester
authors.initials: E
authors.lastname: Campanario
authors.forename: Leandro
authors.initials: L
authors.lastname: Sastre
authors.forename: Jose L
authors.initials: JL
authors.lastname: Martinez
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics*; D003470:Culture Media; D004023:Dictyostelium / Q000235:genetics / Q000254:growth & development; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000096:biosynthesis* / Q000235:genetics*; D010641:Phenotype; D020615:Stenotrophomonas maltophilia / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D014774:Virulence / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D003470:Culture Media; D026901:Membrane Transport Proteins; C417265:SmeD protein, Stenotrophomonas maltophilia; C417266:SmeE protein, Stenotrophomonas maltophilia; C417267:SmeF protein, Stenotrophomonas maltophilia