JAC Advance Access originally published online on October 8, 2002
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Journal of Antimicrobial Chemotherapy (2002) 50, 657-664
© 2002 The British Society for Antimicrobial Chemotherapy
Fitness of in vitro selected Pseudomonas aeruginosa nalB and nfxB multidrug resistant mutants
1 Departamento de Biotecnología Microbiana, Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid; 2 Museo Nacional de Ciencias Naturales (CSIC), Madrid; 3 Servicio de Microbiología, Hospital Ramón y Cajal, Madrid, Spain
Received 14 May 2002; accepted 18 July 2002
Overproduction of multidrug resistance (MDR) efflux pumps is involved in the resistance to a wide range of compounds in bacteria. These determinants extrude antibiotics, but also bacterial metabolites like quorum-sensing signals. Non-regulated extrusion of bacterial metabolites might produce a metabolic burden, so that MDR-overproducing mutants could have a reduced fitness when compared with their parental strains. To test such a possibility, we have compared the behaviour of two MDR Pseudomonas aeruginosa in vitro selected mutants (nalB and nfxB) with their isogenic parental strain with respect to some properties with potential relevance for the survival in the environment and the virulence of this bacterial species. Overproduction of the MDR determinants MexABOprM (nalB mutant) and MexCDOprJ (nfxB mutant) decreased the survival in water, the production of phenazines and proteases, and the virulence (using a Caenorhabditis elegans model system) of the P. aeruginosa mutants. In contrast, the capability of forming biofilms was not impaired. The simple models tested in the present work can enable the analysis of the fitness of large numbers of antibiotic-resistant bacteria by using more realistic approaches than the in vitro competition assays currently used.
Keywords: multidrug resistance, efflux pump, Pseudomonas aeruginosa, bacterial fitness, cost of resistance
* Corresponding author. Tel: +34-91-5854571; Fax: +34-91-5854506; E-mail: jlmtnez{at}cnb.uam.es
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