A New Lineage of <named-content content-type="genus-species">Cryptococcus gattii</named-content> (VGV) Discovered in the Central Zambezian Miombo Woodlands
Rhys A. Farrer,
Miwha Chang,
Michael J. Davis,
Lucy van Dorp,
Dong-Hoon Yang,
Terrance Shea,
Thomas R. Sewell,
Wieland Meyer,
Francois Balloux,
Hannah M. Edwards,
Duncan Chanda,
Geoffrey Kwenda,
Mathieu Vanhove,
Yun C. Chang,
Christina A. Cuomo,
Matthew C. Fisher,
Kyung J. Kwon-Chung
Affiliations
Rhys A. Farrer
Medical Research Council Centre for Medical Mycology, University of Exeter, Exeter, United Kingdom
Miwha Chang
Molecular Microbiology Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
Michael J. Davis
Molecular Microbiology Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
Lucy van Dorp
UCL Genetics Institute, University College London, London, United Kingdom
Dong-Hoon Yang
Molecular Microbiology Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
Terrance Shea
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
Thomas R. Sewell
MRC Centre for Global Infectious Disease Analysis, Imperial College London, London, United Kingdom
Wieland Meyer
Molecular Mycology Research Laboratory, Centre for Infectious Diseases and Microbiology, Faculty of Medicine and Health, Sydney Medical School, Westmead Clinical School, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, NSW, Australia
Francois Balloux
UCL Genetics Institute, University College London, London, United Kingdom
Hannah M. Edwards
MRC Centre for Global Infectious Disease Analysis, Imperial College London, London, United Kingdom
Duncan Chanda
Adult Centre of Excellence, University Teaching Hospital, Lusaka, Zambia
Geoffrey Kwenda
Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, Zambia
Mathieu Vanhove
MRC Centre for Global Infectious Disease Analysis, Imperial College London, London, United Kingdom
Yun C. Chang
Molecular Microbiology Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
Christina A. Cuomo
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
Matthew C. Fisher
MRC Centre for Global Infectious Disease Analysis, Imperial College London, London, United Kingdom
Kyung J. Kwon-Chung
Molecular Microbiology Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
ABSTRACT We discovered a new lineage of the globally important fungal pathogen Cryptococcus gattii on the basis of analysis of six isolates collected from three locations spanning the Central Miombo Woodlands of Zambia, Africa. All isolates were from environments (middens and tree holes) that are associated with a small mammal, the African hyrax. Phylogenetic and population genetic analyses confirmed that these isolates form a distinct, deeply divergent lineage, which we name VGV. VGV comprises two subclades (A and B) that are capable of causing mild lung infection with negligible neurotropism in mice. Comparing the VGV genome to previously identified lineages of C. gattii revealed a unique suite of genes together with gene loss and inversion events. However, standard URA5 restriction fragment length polymorphism (RFLP) analysis could not distinguish between VGV and VGIV isolates. We therefore developed a new URA5 RFLP method that can reliably identify the newly described lineage. Our work highlights how sampling understudied ecological regions alongside genomic and functional characterization can broaden our understanding of the evolution and ecology of major global pathogens. IMPORTANCE Cryptococcus gattii is an environmental pathogen that causes severe systemic infection in immunocompetent individuals more often than in immunocompromised humans. Over the past 2 decades, researchers have shown that C. gattii falls within four genetically distinct major lineages. By combining field work from an understudied ecological region (the Central Miombo Woodlands of Zambia, Africa), genome sequencing and assemblies, phylogenetic and population genetic analyses, and phenotypic characterization (morphology, histopathological, drug-sensitivity, survival experiments), we discovered a hitherto unknown lineage, which we name VGV (variety gattii five). The discovery of a new lineage from an understudied ecological region has far-reaching implications for the study and understanding of fungal pathogens and diseases they cause.
