Zur: Zinc-Sensing Transcriptional Regulator in a Diverse Set of Bacterial Species

Abstract

Zinc (Zn) is the quintessential d block metal, needed for survival in all living organisms. While Zn is an essential element, its excess is deleterious, therefore, maintenance of its intracellular concentrations is needed for survival. The living organisms, during the course of evolution, developed proteins that can track the limitation or excess of necessary metal ions, thus providing survival benefits under variable environmental conditions. Zinc uptake regulator (Zur) is a regulatory transcriptional factor of the FUR superfamily of proteins, abundant among the bacterial species and known for its intracellular Zn sensing ability. In this study, we highlight the roles played by Zur in maintaining the Zn levels in various bacterial species as well as the fact that in recent years Zur has emerged not only as a Zn homeostatic regulator but also as a protein involved directly or indirectly in virulence of some pathogens. This functional aspect of Zur could be exploited in the ventures for the identification of newer antimicrobial targets. Despite extensive research on Zur, the insights into its overall regulon and its moonlighting functions in various pathogens yet remain to be explored. Here in this review, we aim to summarise the disparate functional aspects of Zur proteins present in various bacterial species.

Strategies for Zinc Uptake in Pseudomonas aeruginosa at the Host–Pathogen Interface

“…As a result, the resistance of bacteria to antimicrobial substances and host immune response are improved ( Rahman and Karim, 2017 ). Furthermore, studies have shown that zinc promotes biofilm formation in P. aeruginosa and Xylella fastidiosa , which leads to difficulty in eradicating pathogens from the host ( Kumar et al, 2017 ; Kandari et al, 2021 ). Interestingly, Zn 2+ can also regulate transcription of RNA via regulation of the activity of transcription factors and several enzymes, such as RNA and DNA polymerases ( Nejdl et al, 2014 ).…”

“…Extracellularly, members of the S100 protein family, such as calgranulin C, sequester zinc to inhibit microbial growth. In the face of these nutritional limitations, bacteria rely on an efficient zinc transport system to maintain zinc supplementation for proliferation and disruption of the host defense system to establish infection ( Figure 1 ; Schalk and Cunrath, 2016 ; Gonzalez et al, 2018 ; Cuajungco et al, 2021 ; Kandari et al, 2021 ).…”

“…Because of its strong resistance to a variety of antibiotics, P. aeruginosa brings great challenges to clinical treatment. During infection, P. aeruginosa activates the nutritional immune response in the host, resulting in the chelation of essential elements such as zinc by a variety of host proteins ( Azam and Khan, 2019 ; Kandari et al, 2021 ; Vermilyea et al, 2021 ). Therefore, to ensure successful infection, P. aeruginosa must adapt to zinc-deficient environments, and this process is mainly mediated by zinc uptake systems ( Maares and Haase, 2016 ; Schalk and Cunrath, 2016 ; Gonzalez et al, 2018 ; Kandari et al, 2021 ).…”

“…During infection, P. aeruginosa activates the nutritional immune response in the host, resulting in the chelation of essential elements such as zinc by a variety of host proteins ( Azam and Khan, 2019 ; Kandari et al, 2021 ; Vermilyea et al, 2021 ). Therefore, to ensure successful infection, P. aeruginosa must adapt to zinc-deficient environments, and this process is mainly mediated by zinc uptake systems ( Maares and Haase, 2016 ; Schalk and Cunrath, 2016 ; Gonzalez et al, 2018 ; Kandari et al, 2021 ). At present, there are three known zinc uptake systems in P. aeruginosa , ZnuBC, HmtA, and ZrmABCD ( Figure 2 ), which are all regulated by the Zur protein ( Lewinson et al, 2009 ; Ellison et al, 2013 ).…”

“…Zinc uptake regulator is a zinc-sensing transcriptional regulator that belongs to the Fur superfamily of metal-sensing transcriptional regulators ( Kandari et al, 2021 ). This regulator functions as either a repressor or an activator ( Mikhaylina et al, 2018 ) and regulates the expression of a large number of genes in bacteria, including those responsible for zinc import and zinc export, as well as chaperone proteins, metallochaperones, enzymes, virulence factors, and some ribosomal proteins ( Fillat, 2014 ).…”