title: 'Division of labour' in response to host oxidative burst drives a fatal Cryptococcus gattii outbreak.
abstract: Cryptococcus gattii is an emerging intracellular pathogen and the cause of the largest primary outbreak of a life-threatening fungal disease in a healthy population. Outbreak strains share a unique mitochondrial gene expression profile and an increased ability to tubularize their mitochondria within host macrophages. However, the underlying mechanism that causes this lineage of C. gattii to be virulent in immunocompetent individuals remains unexplained. Here we show that a subpopulation of intracellular C. gattii adopts a tubular mitochondrial morphology in response to host reactive oxygen species. These fungal cells then facilitate the rapid growth of neighbouring C. gattii cells with non-tubular mitochondria, allowing for effective establishment of the pathogen within a macrophage intracellular niche. Thus, host reactive oxygen species, an essential component of the innate immune response, act as major signalling molecules to trigger a 'division of labour' in the intracellular fungal population, leading to increased pathogenesis within this outbreak lineage.
authors.affiliation: 1] Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, West Midlands, Birmingham B15 2TT, UK [2] National Institute of Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, UK.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Voelz
authors.affiliation: 1] Department of Infection and Immunity, University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK [2] Bateson Centre, Department of Biomedical Sciences, University of Sheffield, Firth Court, Western Bank S10 2TN, UK.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Johnston
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, West Midlands, Birmingham B15 2TT, UK.
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Smith
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, West Midlands, Birmingham B15 2TT, UK.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Hall
authors.affiliation: School of Biological Sciences, University of Missouri, Kansas City, Missouri 64110, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Idnurm
authors.affiliation: 1] Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, West Midlands, Birmingham B15 2TT, UK [2] National Institute of Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, UK.
authors.forename: Robin C
authors.initials: RC
authors.lastname: May
mesh_terms: D000818:Animals; D001343:Autophagy; D002460:Cell Line; D049109:Cell Proliferation; D003453:Cryptococcosis / Q000276:immunology* / Q000382:microbiology; D056285:Cryptococcus gattii / Q000472:pathogenicity*; D004195:Disease Models, Animal; D004196:Disease Outbreaks; D005838:Genotype; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst
chemical_list: D017382:Reactive Oxygen Species; D049452:Green Fluorescent Proteins; D020928:Mitogen-Activated Protein Kinases