Host-Imposed Copper Poisoning Impacts Fungal Micronutrient Acquisition during Systemic Candida albicans Infections

• DOI: 10.1371/journal.pone.0158683
• Publication Date: 2016-06-30T19:47:23Z
• Authors: Joanna Mackie; Edina K. Szabo; Dagmar S. Urgast; Elizabeth R. Ballou; Delma S. Childers; Donna M. MacCallum; Joerg Feldmann; Alistair J. P. Brown
• Keywords: MR/N006364/1; Supplementary Data; Science; 610; R Medicine; Kidney; Mass Spectrometry; Fungal Proteins; Mice; 03 medical and health sciences; Gene Expression Regulation, Fungal; Candida albicans; Animals; Homeostasis; Wellcome Trust; 0303 health sciences; Virulence; BB/F00513X/1; Gene Expression Profiling; Q; R; Candidiasis; BB/K017365/1; Medical Research Council (MRC); ERC-2009-AdG-249793; Disease Models, Animal; Oxidative Stress; 097377; Liver; MR/M026663/1; Biotechnology and Biological Sciences Research Council (BBSRC); Disease Progression; Medicine; Copper; Spleen; European Research Council; Research Article

Nutritional immunity is a process whereby an infected host manipulates essential micronutrients to defend against invading pathogen. We reveal dynamic aspect of nutritional during infection that involves copper assimilation. Using combination laser ablation inductively coupled mass spectrometry (LA-ICP MS) and metal mapping, immunohistochemistry, gene expression profiling from tissues, we show readjustments in hepatic, splenic renal homeostasis accompany disseminated Candida albicans infections the mouse model. Localized host-imposed poisoning manifests itself as transient increase early kidney infection. Changes are detected by fungus, revealed fungal virulence studies. The fungus responds differentially regulating Crp1 efflux pump (higher down-regulation late infection) Ctr1 importer (lower infection, subsequent up-regulation maintain disease progression. Both required for full virulence. Importantly, influences other traits—metabolic flexibility oxidative stress resistance. Our study highlights importance defence systemic disease.