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

Lay Summary

Zn has tremendous importance in all life forms. Since it is essential but deleterious in excess, during the course of evolution, the living organisms have devised strategies or regulatory mechanisms to cope up with the fluctuations in concentrations of this metal. Interestingly, the mechanisms of regulation are usually different in prokaryotes and eukaryotes. Apparently, such bacterium-specific mechanisms can be employed to target the pathogen inhabiting the human system. Zur is one such prokaryotic transcriptional regulator whose function typically is to maintain Zn homeostasis but otherwise it does have certain moonlighting functions that make it an interesting protein to study. The point of the review is to know the structure and molecular mechanisms of Zur and to enlist the bacterial species that possess this protein, along with those that have it but are still waiting to be investigated. Additionally, we have touched upon the instances wherein this protein assists and helps evade many pathogens from the wrath of host-mediated nutritional immunity.
The motive was to look for the various roles that Zur plays, specifically in the pathogens. We have tried to touch upon as many pathogens as possible and have highlighted the crucial role that Zur plays for them. We would want to draw attention to those pathogens, in which the potential of this protein await investigation as far as its moonlighting functions are concerned. While concluding, we also hypothesize that this protein is not merely a Zn-dependent transcriptional regulator, rather, it is a master protein that is key for survival in many pathogens, and that it could be a potential antimicrobial target, but this fact certainly merits further investigation.

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.

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