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

Shuaitao Wang,Xiangqian Zhang,Jinshui Lin,Juanli Cheng,Yanting Niu,Panxin Li

doi:10.3389/fmicb.2021.741873

Abstract

As a structural, catalytic, and signaling component, zinc is necessary for the growth and development of plants, animals, and microorganisms. Zinc is also essential for the growth of pathogenic microorganisms and is involved in their metabolism as well as the regulation of various virulence factors. Additionally, zinc is necessary for infection and colonization of pathogenic microorganisms in the host. Upon infection in healthy organisms, the host sequesters zinc both intracellularly and extracellularly to enhance the immune response and prevent the proliferation and infection of the pathogen. Intracellularly, the host manipulates zinc levels through Zrt/Irt-like protein (ZIP)/ZnT family proteins and various zinc storage proteins. 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. Here, we summarize the strategies for zinc uptake in conditional pathogenic Pseudomonas aeruginosa, including known zinc uptake systems (ZnuABC, HmtA, and ZrmABCD) and the zinc uptake regulator (Zur). In addition, other potential zinc uptake pathways were analyzed. This review systematically summarizes the process of zinc uptake by P. aeruginosa to provide guidance for the development of new drug targets.

Highlights

The ions of numerous metals, notably magnesium, calcium, zinc, iron, manganese, and copper, play numerous biological roles as both structural and catalytic cofactors for proteins (Andreini et al, 2008)
We focus on the introduction of three known zinc uptake systems (ZnuABC, HmtA, and ZrmABCD) and zinc uptake regulator (Zur) in P. aeruginosa while discussing other potential zinc uptake systems
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)

Summary

Introduction

The ions of numerous metals, notably magnesium, calcium, zinc, iron, manganese, and copper, play numerous biological roles as both structural and catalytic cofactors for proteins (Andreini et al, 2008). It is estimated that the activity of one in three proteins requires metal ions (Gray, 2003; Dupont et al, 2006) These metal ions are essential to microbial pathogens during infection because they are involved in bacterial. Vertebrate hosts exploit the requirement for nutrient metals by limiting their availability, which is a process termed ‘nutritional immunity’ (Kehl-Fie et al, 2011). This restriction starves invaders of these essential metals, thereby inactivating metal-dependent processes, reducing bacterial growth, and rendering them more sensitive to other aspects of the immune response (Grim et al, 2017). Originally associated only with iron restriction, it is known that other metals, including zinc and manganese, are sequestered during infection (Juttukonda and Skaar, 2017)

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Conclusion