Affiliation:
1. Department of Botany and Plant Biology, Sciences III
2. Department of Microbiology and Molecular Medicine, Centre Médical Universitaire, University of Geneva, Geneva, Switzerland
Abstract
ABSTRACT
The effects of copper (Cu) on trace metal and antibiotic resistance of
Pseudomonas aeruginosa
have been investigated. Cu treatments induced resistance not only to this metal but also, surprisingly, to zinc (Zn). Quantitative reverse transcription-PCR (qRT-PCR) revealed that after Cu treatment the transcription of the
czcRS
two-component system (TCS) operon was enhanced as well as that of the
czcCBA
operon encoding an efflux pump specific for zinc, cadmium, and cobalt. Cu treatments at the same time caused a decrease in the production of OprD porin, resulting in resistance to the carbapenem antibiotic imipenem. The CzcR regulator was known to repress
oprD
. However, Cu was still able to decrease the production of OprD and induce imipenem resistance in a
czcRS
knockout mutant. This strongly suggested that another Cu-dependent regulatory system was acting negatively on
oprD
expression. TCS regulator genes
copR-copS
have been shown to be involved in Cu tolerance in
P. aeruginosa
. qRT-PCR showed that overproduction of the CopR or of the CzcR regulator resulted in increased transcription of the
czcC
gene as well as in a decrease in
oprD
gene transcription, either in the wild-type strain or in the
czcRS
knockout mutant. Overproduction experiments suggest that a metal-dependent mechanism operates at the posttranscriptional level to control the production of the CzcCBA efflux pump. This study shows that CopR is a new negative regulator of OprD porin and that it links Zn, Cu, and imipenem resistances by interacting with the CzcRS TCS.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
143 articles.
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