Copper microenvironments in the human body define patterns of copper adaptation in pathogenic bacteria

Focarelli, F, Giachino, A ORCID: and Waldron, KJ 2022, 'Copper microenvironments in the human body define patterns of copper adaptation in pathogenic bacteria' , PLOS Pathogens .

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Copper is an essential micronutrient for most organisms that is required as a cofactor for crucial copper-dependent enzymes encoded by both prokaryotes and eukaryotes. Evidence accumulated over several decades has shown that copper plays important roles in the function of the mammalian immune system. Copper accumulates at sites of infection, including the gastrointestinal and respiratory tracts and in blood and urine, and its antibacterial toxicity is directly leveraged by phagocytic cells to kill pathogens. Copper-deficient animals are more susceptible to infection, whereas those fed copper-rich diets are more resistant. As a result, copper resistance genes are important virulence factors for bacterial pathogens, enabling them to detoxify the copper insult while maintaining copper supply to their essential cuproenzymes. Here, we describe the accumulated evidence for the varied roles of copper in the mammalian response to infections, demonstrating that this metal has numerous direct and indirect effects on immune function. We further illustrate the multifaceted response of pathogenic bacteria to the elevated copper concentrations that they experience when invading the host, describing both conserved and species-specific adaptations to copper toxicity. Together, these observations demonstrate the roles of copper at the host–pathogen interface and illustrate why bacterial copper detoxification systems can be viable targets for the future development of novel antibiotic drug development programs.</jats:p>

Item Type: Article
Schools: Schools > School of Environment and Life Sciences
Journal or Publication Title: PLOS Pathogens
Publisher: Public Library of Science
ISSN: 1553-7374
Funders: Biotechnology and Biological Sciences Research Council, Newcastle University’s Faculty of Medical Sciences
Depositing User: A Giachino
Date Deposited: 01 Nov 2022 08:58
Last Modified: 01 Nov 2022 09:00

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