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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.

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.

journal_name

Environ Microbiol

journal_title

Environmental microbiology

authors

Olivares J,Alvarez-Ortega C,Linares JF,Rojo F,Köhler T,Martínez JL

doi

10.1111/j.1462-2920.2012.02727.x

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

1968-81

issue

eissn

1462-2912

issn

1462-2920

journal_volume

pub_type

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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.