title: Genomic epidemiology of Cryptococcus yeasts identifies adaptation to environmental niches underpinning infection across an African HIV/AIDS cohort.
abstract: Emerging infections caused by fungi have become a widely recognized global phenomenon and are causing an increasing burden of disease. Genomic techniques are providing new insights into the structure of fungal populations, revealing hitherto undescribed fine-scale adaptations to environments and hosts that govern their emergence as infections. Cryptococcal meningitis is a neglected tropical disease that is responsible for a large proportion of AIDS-related deaths across Africa; however, the ecological determinants that underlie a patient's risk of infection remain largely unexplored. Here, we use genome sequencing and ecological genomics to decipher the evolutionary ecology of the aetiological agents of cryptococcal meningitis, Cryptococcus neoformans and Cryptococcus gattii, across the central African country of Zambia. We show that the occurrence of these two pathogens is differentially associated with biotic (macroecological) and abiotic (physical) factors across two key African ecoregions, Central Miombo woodlands and Zambezi Mopane woodlands. We show that speciation of Cryptococcus has resulted in adaptation to occupy different ecological niches, with C. neoformans found to occupy Zambezi Mopane woodlands and C. gattii primarily recovered from Central Miombo woodlands. Genome sequencing shows that C. neoformans causes 95% of human infections in this region, of which over three-quarters belonged to the globalized lineage VNI. We show that VNI infections are largely associated with urbanized populations in Zambia. Conversely, the majority of C. neoformans isolates recovered in the environment belong to the genetically diverse African-endemic lineage VNB, and we show hitherto unmapped levels of genomic diversity within this lineage. Our results reveal the complex evolutionary ecology that underpins the reservoirs of infection for this, and likely other, deadly pathogenic fungi.
authors.affiliation: Department of Infectious Disease Epidemiology, St Mary's Hospital, Imperial College London, London, W2 1PG, UK.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vanhove
authors.affiliation: Department of Infectious Disease Epidemiology, St Mary's Hospital, Imperial College London, London, W2 1PG, UK.|Institute of Infection and Immunity, St. George's University of London, Blackshaw Road, London SW17 0QT, UK.|Division of Infection & Immunity, University College London, Gower St, London WC1E 6BT, UK.
authors.forename: Mathew A
authors.initials: MA
authors.lastname: Beale
authors.affiliation: Department of Infectious Disease Epidemiology, St Mary's Hospital, Imperial College London, London, W2 1PG, UK.
authors.forename: Johanna
authors.initials: J
authors.lastname: Rhodes
authors.affiliation: School of Medicine, University of Zambia, Nationalist Road, PO Box 50110, Lusaka, Zambia.
authors.forename: Duncan
authors.initials: D
authors.lastname: Chanda
authors.affiliation: School of Medicine, University of Zambia, Nationalist Road, PO Box 50110, Lusaka, Zambia.
authors.forename: Shabir
authors.initials: S
authors.lastname: Lakhi
authors.affiliation: Department of Biomedical Sciences, University of Zambia, PO Box 32379, Lusaka, Zambia.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Kwenda
authors.affiliation: Institute of Infection and Immunity, St. George's University of London, Blackshaw Road, London SW17 0QT, UK.
authors.forename: Sile
authors.initials: S
authors.lastname: Molloy
authors.affiliation: Institute of Infection and Immunity, St. George's University of London, Blackshaw Road, London SW17 0QT, UK.
authors.forename: Natasha
authors.initials: N
authors.lastname: Karunaharan
authors.affiliation: Institute of Infection and Immunity, St. George's University of London, Blackshaw Road, London SW17 0QT, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Stone
authors.affiliation: Institute of Infection and Immunity, St. George's University of London, Blackshaw Road, London SW17 0QT, UK.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Harrison
authors.affiliation: Institute of Infection and Immunity, St. George's University of London, Blackshaw Road, London SW17 0QT, UK.
authors.forename: Tihana
authors.initials: T
authors.lastname: Bicanic
authors.affiliation: Department of Infectious Disease Epidemiology, St Mary's Hospital, Imperial College London, London, W2 1PG, UK.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Fisher
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D056285:Cryptococcus gattii / Q000235:genetics*; D003455:Cryptococcus neoformans / Q000235:genetics*; D058893:DNA Barcoding, Taxonomic; D004271:DNA, Fungal / Q000235:genetics; D021903:DNA, Ribosomal Spacer / Q000235:genetics; D065928:Forests; D005828:Genetics, Population; D016681:Genome, Fungal; D023281:Genomics; D006801:Humans; D016919:Meningitis, Cryptococcal / Q000453:epidemiology / Q000382:microbiology*; D008954:Models, Biological; D010802:Phylogeny; D024301:Plant Bark / Q000382:microbiology; D020641:Polymorphism, Single Nucleotide; D012988:Soil Microbiology; D014197:Trees / Q000382:microbiology; D015024:Zambia
chemical_list: D004271:DNA, Fungal; D021903:DNA, Ribosomal Spacer
keywords: 
  Cryptococcus neoformans
  ; ecological genetics; fungi; microbial ecology; niche modelling