title: Metal ion homeostasis in Listeria monocytogenes and importance in host-pathogen interactions.
abstract: Listeria monocytogenes is responsible for one of the most life-threatening food-borne infections and the leading cause of food-poisoning associated deaths in the UK. Infection may be of the unborn/newly born infant where disease may manifest as listeric abortion, stillbirth or late-onset neonatal listeriosis, while in adults, infection usually affects the central nervous system causing meningitis. Crucial to the survival of L. monocytogenes, both inside and outside the host, is its ability to acquire metals which act as cofactors for a broad range of its cellular proteins. However, L. monocytogenes must also protect itself against the innate toxicity of metals. The importance of metals in host-pathogen interactions is illustrated by the restriction of metals (including zinc and iron) in vertebrates in response to infection and the use of high levels of metals (copper and zinc) as part of the antimicrobial defences within host phagocytes. As such, L. monocytogenes is equipped with various mechanisms to tightly control its cellular metal pools and avoid metal poisoning. These include multiple DNA-binding metal-responsive transcription factors, metal-acquisition, metal-detoxification and metal-storage systems, some of which represent key L. monocytogenes virulence determinants. This review discusses current knowledge of the role of metals in L. monocytogenes infections, with a focus on the mechanisms that contribute to zinc and copper homeostasis in this organism. The requirement to precisely control cellular metal levels may impose a vulnerability to L. monocytogenes which can be exploited in antimicrobials and therapeutics.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Jesse
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Roberts
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom. Electronic address: jennifer.s.cavet@manchester.ac.uk.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Cavet
mesh_terms: D000818:Animals; D003300:Copper / Q000378:metabolism*; D006706:Homeostasis; D054884:Host-Pathogen Interactions; D006801:Humans; D008089:Listeria monocytogenes / Q000502:physiology*; D008088:Listeriosis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D015032:Zinc / Q000378:metabolism*
chemical_list: D003300:Copper; D015032:Zinc
keywords: Bacterial pathogenicity; CopA; CopZ; Copper; CsoR; ZinABC; Zinc; ZnuABC; Zur