Zinc homeostasis in Pseudomonas

Ducret, Véréna; González, Diego; Perron, Karl

doi:10.1007/s10534-022-00475-5

Cited by 19 publications

(20 citation statements)

References 94 publications

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“…The Zur protein, when concentrations of Zn are sufficient or excessive, binds to a 17 bp DNA Zur box to repress genes involved in Zn import [17]. In a global bioinformatics search on the P. aeruginosa genome, we found, as expected, Zur boxes in the promoter regions of genes involved in the import of Zn, but also, intriguingly, upstream of the czcRS genes [8]. This suggested a possible direct regulatory link, mediated by Zur, between the import and export of Zn.…”

Section: Zur Binds To the Czcrs Promotersupporting

confidence: 69%

“…Interestingly, among the Pseudomonas species analyzed for the presence and location of Zur boxes (i.e. P. chlororaphis, P. fluorescens, P. putida, P. stuzeri and P. syringae), only P. aeruginosa possesses boxes upstream of the czcR gene [8]. This characteristic could be related to its ability to proliferate in presence of high metal concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…In the Gram-negative bacterium Pseudomonas aeruginosa, several systems are involved in Zn homeostasis [7,8]. Zn import into the periplasm is mediated by TonBdependent importers such as ZnuD.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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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.

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Section: Zur Binds To the Czcrs Promotersupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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“…The TCS CzcRS is known to respond to several signals, including zinc stress [33]. We therefore assessed its effect on pcoA2 and cusRS expression in the presence of copper and/or zinc.…”

Section: Resultsmentioning

confidence: 99%

Cross-regulation and cross-talk of conserved and accessory two-component regulatory systems orchestratePseudomonascopper resistance

Elsen,

Simon,

Attrée

2023

Preprint

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Bacteria use diverse strategies and molecular machinery to maintain copper homeostasis and to cope with its toxic effects. Some genetic elements providing copper resistance are acquired by horizontal gene transfer; however, little is known about how they are controlled and integrated into the central regulatory network. Here, we studied two copper-responsive systems in a clinical isolate ofPseudomonas paraeruginosaand deciphered the regulatory and cross-regulation mechanisms. To do so, we combined mutagenesis, transcriptional fusion analyses and copper sensitivity phenotypes. Our results showed that the accessory CusRS two-component system (TCS) responds to copper and activates both its own expression and that of the adjacent nine-gene operon to provide resistance to elevated levels of extracellular copper. The same locus was also found to be regulated by two core-genome-encoded TCSs - the copper-responsive CopRS and the zinc-responsive CzcRS. Although the target palindromic sequence – ATTCATnnATGTAAT – is the same for the three response regulators, transcriptional outcomes differ. Thus, depending on the operon/regulator pair, binding can result in different activation levels (from none to high), with the systems demonstrating considerable plasticity. Unexpectedly, although the classical CusRS and the noncanonical CopRS TCSs rely on distinct signaling mechanisms (kinase-basedvs. phosphatase-based), we discovered cross-talk in the absence of the cognate sensory kinases. This cross-talk occurred between the proteins of these two otherwise independent systems. The entire locus is part of an Integrative and Conjugative Element, and was found in otherPseudomonasstrains where its expression could provide copper resistance under appropriate conditions. The results presented here illustrate how acquired genetic elements can become part of endogenous regulatory networks, providing a physiological advantage. They also highlight the potential for broader effects of accessory regulatory proteins through interference with core regulatory proteins.Author SummaryTwo-component regulatory systems play a key role in bacterial life by detecting and integrating a wide range of signals, allowing bacteria to continuously monitor and adapt to a changing environment. They weave a complex network with a few highly interconnected phosphorelays and numerous cross-regulations. Our study reveals connections between zinc and copper homeostasis in a pathogenic bacterium, with cross-regulation observed for three independent, closely related transcriptional regulators, CzcR, CopR and CusR. Zinc and copper play a major role in host-pathogen interactions, and bacteria that synergize their responses to the two elements can harness a growth advantage and enhanced fitness in specific conditions. We also observed unexpected cross-talk between the core genome-encoded CopRS system and the horizontally acquired CusRS system, although the molecular control exerted by a histidine kinase on its cognate regulator differs. This plasticity observed within the two signaling systems ensures a normal regulatory response to the copper signal required to maintain copper homeostasis.

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“…The complex consists of an inner membrane protein (CzcA), an outer membrane protein (CzcC) and a protein associated with both membranes (CzcB) ( 69 ). The Zur regulon of E. coli contains four operons: znuABC, zinT, ykgMO and pliG ( 70 , 71 ). Many bacteria such as Paracoccus denitrificans ( 72 ), Mycobacterium tuberculosis ( 73 ) and Bacillus subtilis ( 74 ) contain znuABC or Znu-like members of the ABC superfamily.…”

Section: Discussionmentioning

confidence: 99%

Virulence regulation of Zn2+ uptake system znuABC on mesophilic Aeromonas salmonicida SRW-OG1

et al. 2023

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Psychrophilic Aeromonas salmonicida could not grow above 25°C and therefore thought unable to infect mammals and humans. In our previous study, a mesophilic A. salmonicida SRW-OG1 was isolated from Epinephelus coioides with furunculosis. Through the analysis of preliminary RNA-seq, it was found that the Zn2+ uptake related genes znuA, znuB and znuC might be involved in the virulence regulation of A. salmonicida SRW-OG1. Therefore, the purpose of this study was to explore the effect of znuABC silencing on the virulence regulation of A. salmonicida SRW-OG1. The results showed that the growth of the znuA-RNAi, znuB-RNAi, and znuC-RNAi strains was severely restricted under the Fe2+ starvation, but surprisingly there was no significant difference under the Zn2+ restriction. In the absence of Zn2+ and Fe2+, the expression level of znuABC was significantly increased. The motility, biofilm formation, adhesion and hemolysis of the znuA-RNAi, znuB-RNAi, and znuC-RNAi strains were significantly reduced. We also detected the expression of znuABC under different growth periods, temperatures, pH, as well as Cu2+ and Pb2+ stresses. The results showed that znuABC was significantly up-regulated in the logarithmic phase and the decline phase of A. salmonicida. Interestingly, the trend of expression levels of the znuABC at 18, 28, and 37°C was reversed to another Zn2+ uptake related gene zupT. Taken together, these indicated that the znuABC was necessary for A. salmonicida SRW-OG1 pathogenicity and environmental adaptability, and was cross regulated by iron starvation, but it was not irreplaceable for A. salmonicida SRW-OG1 Zn2+ uptake in the host.

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Zinc homeostasis in Pseudomonas

Cited by 19 publications

References 94 publications

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

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

Cross-regulation and cross-talk of conserved and accessory two-component regulatory systems orchestratePseudomonascopper resistance

Virulence regulation of Zn2+ uptake system znuABC on mesophilic Aeromonas salmonicida SRW-OG1

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