Nutrient Zinc at the Host–Pathogen Interface

• Published in: Trends in biochemical sciences (Amsterdam. Regular ed.) Vol. 44; no. 12; pp. 1041 - 1056
• Main Authors: Lonergan, Zachery R., Skaar, Eric P.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2019
• Subjects: Animals; host-pathogen interactions; Host-Pathogen Interactions - physiology; Humans; Infections - immunology; metals; Nutrients - immunology; nutritional immunity; zinc; Zinc - immunology; metals; host-pathogen interactions; nutritional immunity; zinc
• ISSN: 0968-0004; 1362-4326
• DOI: 10.1016/j.tibs.2019.06.010

Zinc is an essential cofactor required for life and, as such, mechanisms exist for its homeostatic maintenance in biological systems. Despite the evolutionary distance between vertebrates and microbial life, there are parallel mechanisms to balance the essentiality of zinc with its inherent toxicity. Vertebrates regulate zinc homeostasis through a complex network of metal transporters and buffering systems that respond to changes in nutritional zinc availability or inflammation. Fine-tuning of this network becomes crucial during infections, where host nutritional immunity attempts to limit zinc availability to pathogens. However, accumulating evidence demonstrates that pathogens have evolved mechanisms to subvert host-mediated zinc withholding, and these metal homeostasis systems are important for survival within the host. We discuss here the mechanisms of vertebrate and bacterial zinc homeostasis and mobilization, as well as recent developments in our understanding of microbial zinc acquisition. •Zinc is a redox-inactive nutrient metal that is required for the catalytic activity and/or structural stability for thousands of proteins throughout life.•Vertebrate hosts and bacterial pathogens have evolved parallel mechanisms for balancing the essentiality of zinc with its inherent toxicity.•Zinc homeostasis relies on a complex network of metal transporters linked to zinc buffering systems.•Members of a GTPase subfamily are implicated as zinc-specific metallochaperones which aid metal delivery to cognate metalloenzymes.