A Zur-mediated transcriptional regulation of the zinc export system in Pseudomonas aeruginosa

Abstract

The control of cellular zinc (Zn) concentrations by dedicated import and export systems is essential for the survival and virulence of Pseudomonas aeruginosa. The transcription of its many Zn transporters is therefore tightly regulated by a known set of transcription factors involved in either the import or the export of Zn. In this work, we show that the Zur protein, a well-known repressor of Zn import, plays a dual role and functions in both import and export processes. In a situation of Zn excess, Zur represses Zn entry, but also activates the transcription of czcR, a positive regulator of the Zn export system. To achieve this, Zur binds at two sites, located by DNA footprinting in the region downstream the czcR transcription start site. In agreement with this regulation, a delay in induction of the efflux system is observed in the absence of Zur and Zn resistance is reduced. The discovery of this regulation highlights a new role of Zur as global regulator of Zn homeostasis in P. aeruginosa disclosing an important link between Zur and zinc export.

Antimicrobial Resistance: Two-Component Regulatory Systems and Multidrug Efflux Pumps

“…Furthermore, the Z inc U ptake R egulator (also known as Zur protein) has been shown to be involved in the control of intracellular zinc by the activation of CzcR. Indeed, in the presence of high quantities of Zn inside the bacterial cell, Zur dimerizes with zinc and enhances the expression of the regulator CzcR that, in turn, promotes the up-regulation of the zinc-extruding efflux pump CzcCBA [ 198 ]. CzcRS-dependent zinc induction plays a relevant role in P. aeruginosa since urine can release zinc upon contact with siliconized latex urinary catheters favoring carbepenem-resistance mediated by OprD expression [ 199 , 200 ].…”