Molecular Evolution of Transition Metal Bioavailability at the Host–Pathogen Interface

The molecular evolution of the adaptive response at the host–pathogen interface has been frequently referred to as an 'arms race' between the host and bacterial pathogens. The innate immune system employs multiple strategies to starve microbes of metals. Pathogens, in turn, develop success...

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Bibliographic Details
Published in:Trends in microbiology (Regular ed.) 2021-05, Vol.29 (5), p.441-457
Main Authors: Antelo, Giuliano T., Vila, Alejandro J., Giedroc, David P., Capdevila, Daiana A.
Format: Article
Language:English
Subjects:
Allosteric properties
Antibiotics
Bacteria
Bacteria - genetics
Bacteria - metabolism
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Bioavailability
Biological Availability
calprotectin
Chelation
Coevolution
Evolution
Evolution, Molecular
Heavy metals
Heme
Host-Pathogen Interactions - genetics
Host-Pathogen Interactions - physiology
Humans
Immune system
Immunity
Innate immunity
Lactoferrin
Macrophages
Metal ions
metallo-β-lactamases
Metallography
metalloregulator
metallostasis
Metals
Metals - metabolism
Molecular evolution
Nramp protein
nutritional immunity
Pathogens
Proteins
Regulatory proteins
Siderophores
Transcription
Transferrin
Transition metals
Zinc metalloenzyme
β Lactamase
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Summary:The molecular evolution of the adaptive response at the host–pathogen interface has been frequently referred to as an 'arms race' between the host and bacterial pathogens. The innate immune system employs multiple strategies to starve microbes of metals. Pathogens, in turn, develop successful strategies to maintain access to bioavailable metal ions under conditions of extreme restriction of transition metals, or nutritional immunity. However, the processes by which evolution repurposes or re-engineers host and pathogen proteins to perform or refine new functions have been explored only recently. Here we review the molecular evolution of several human metalloproteins charged with restricting bacterial access to transition metals. These include the transition metal-chelating S100 proteins, natural resistance-associated macrophage protein-1 (NRAMP-1), transferrin, lactoferrin, and heme-binding proteins. We examine their coevolution with bacterial transition metal acquisition systems, involving siderophores and membrane-spanning metal importers, and the biological specificity of allosteric transcriptional regulatory proteins tasked with maintaining bacterial metallostasis. We also discuss the evolution of metallo-β-lactamases; this illustrates how rapid antibiotic-mediated evolution of a zinc metalloenzyme obligatorily occurs in the context of host-imposed nutritional immunity. The interaction between human iron-transport proteins and bacterial receptors acts as a driving force for the diversification of both families of proteins.Calprotectin, a pivotal nutritional immunity protein, evolved from a family of proinflammatory proteins that developed high-affinity binding sites for transition metals.Plasticity of siderophore importers allows for nutritional iron acquisition by bacterial cheaters, which, in turn, selects for diversification of siderophore biosynthetic pathways in producers.Comparative studies of inorganic sensors from the same structural class provide insights into the evolution of functional diversity in regulators of metallostasis.ZnII-binding affinity and apo-protein stability of periplasmic metallo-β-lactamases are key evolutionary traits of these enzymes in the context of nutritional immunity.
ISSN:0966-842X
1878-4380
1878-4380
DOI:10.1016/j.tim.2020.08.001