Overproduction of the multidrug efflux pump MexEF-OprN does not impair Pseudomonas aeruginosa fitness in competition tests, but produces specific changes in bacterial regulatory networks

JORGE ANDRES OLIVARES PACHECO, Carolina Alvarez-Ortega, Juan F. Linares, Fernando Rojo, Thilo Köhler, José Luis Martínez

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

It is generally assumed that acquisition of antibiotic resistance leads to non-specific fitness costs. We have tested the alternative hypothesis that acquisition of antibiotic resistance may not always produce a general burden to the microorganisms, as measured in competition tests, but rather lead to specific changes in bacterial physiology. To this end we studied the effect of overproducing the multidrug efflux pump MexEF-OprN on Pseudomonas aeruginosa due to a constitutive activation of MexT, the transcriptional activator of the mexEF-oprN genes. We found that overexpression of MexEF-OprN does not cause a significant decrease in P. aeruginosa fitness in classical competition tests, indicating the absence of a large metabolic burden and that any possible negative effects might be observed only under specific conditions. Transcriptomic analyses revealed that overexpression of MexEF-OprN results in reduced expression of several quorum-sensing regulated genes. We traced back this phenotype to a delay in PQS production due to extrusion of kynurenine, a PQS precursor, through the efflux pump. Type VI secretion was also impaired. A Caenorhabditis elegans model demonstrated that overproduction of MexEF-OprN impairs virulence in P. aeruginosa. This effect was mainly due to the activity of the efflux pump, and not to MexT, despite the fact that the latter regulates Type III and Type VI secretion. Altogether, these data indicate that antibiotic resistance can produce modifications in the bacterial regulatory networks with relevant consequences for the bacterial behaviour in specific ecosystems, including the infected host.

Original languageEnglish
Pages (from-to)1968-1981
Number of pages14
JournalEnvironmental Microbiology
Volume14
Issue number8
DOIs
StatePublished - 1 Aug 2012

Fingerprint Dive into the research topics of 'Overproduction of the multidrug efflux pump MexEF-OprN does not impair Pseudomonas aeruginosa fitness in competition tests, but produces specific changes in bacterial regulatory networks'. Together they form a unique fingerprint.

Cite this