Regulation of the mexCD-oprJ multidrug efflux operon in Pseudomonas aeruginosa: characterization of the NfxB-EsrC repressor interaction
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Authors
Mikalauskas, Alaya
Date
2015-09-26
Type
thesis
Language
eng
Keyword
Pseudomonas aeruginosa , MexCD-OprJ , Multidrug resistance , NfxB , EsrC , Efflux
Alternative Title
Abstract
The MexCD-OprJ multidrug efflux pump of Pseudomonas aeruginosa is a RND-type efflux system that is capable of exporting, and thus providing resistance to, multiple classes of clinically-relevant antibiotics such as fluoroquinolones, β-lactams and macrolides. Although quiescent in wild-type P. aeruginosa, mexCD-oprJ is induced by membrane-damaging agents such as detergents and the biocide chlorhexidine (CHX), which perturb the cell envelope. Induction of mexCD-oprJ by membrane-damaging agents requires the envelope stress sigma factor AlgU, an indication that MexCD-OprJ is a component of the envelope stress response in P. aeruginosa. In the absence of CHX-mediated envelope stress, the expression of mexCD-oprJ is regulated solely by the NfxB repressor, which binds as a tetramer to the nfxB-mexC intergenic region to repress transcription of the mexCD-oprJ operon. Recently, a second repressor of mexCD-oprJ with homology to NfxB, EsrC, was discovered. In the absence of CHX-mediated envelope stress, the expression of esrC is negatively regulated by NfxB. In the presence of CHX-mediated envelope stress, the repressor activity of NfxB is alleviated and EsrC is produced, where it contributes to moderate repression of the mexCD-oprJ operon, which is expressed at moderate levels. Interestingly, EsrC requires NfxB in order to act as a repressor of the mexCD-oprJ operon. Consistent with previous research, this study demonstrated a physical interaction between NfxB and EsrC. In addition, this study showed that the C-terminal domains of NfxB and EsrC are required for the NfxB-EsrC interaction to occur. The demonstration of an interaction between NfxB and EsrC suggests that these two repressors co-regulate the expression of the mexCD-oprJ operon in the presence of envelope stress to either prevent the potentially detrimental effects of MexCD-OprJ overexpression, or to modulate mexCD-oprJ expression in response to multiple envelope stress signals which are recognized by the NfxB and EsrC components of the heteromultimeric repressor.
Description
Thesis (Master, Microbiology & Immunology) -- Queen's University, 2015-09-23 10:23:59.344
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ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.