title: Cryptococcus gattii VGIII isolates causing infections in HIV/AIDS patients in Southern California: identification of the local environmental source as arboreal.
abstract: Ongoing Cryptococcus gattii outbreaks in the Western United States and Canada illustrate the impact of environmental reservoirs and both clonal and recombining propagation in driving emergence and expansion of microbial pathogens. C. gattii comprises four distinct molecular types: VGI, VGII, VGIII, and VGIV, with no evidence of nuclear genetic exchange, indicating these represent distinct species. C. gattii VGII isolates are causing the Pacific Northwest outbreak, whereas VGIII isolates frequently infect HIV/AIDS patients in Southern California. VGI, VGII, and VGIII have been isolated from patients and animals in the Western US, suggesting these molecular types occur in the environment. However, only two environmental isolates of C. gattii have ever been reported from California: CBS7750 (VGII) and WM161 (VGIII). The incongruence of frequent clinical presence and uncommon environmental isolation suggests an unknown C. gattii reservoir in California. Here we report frequent isolation of C. gattii VGIII MATα and MATa isolates and infrequent isolation of VGI MATα from environmental sources in Southern California. VGIII isolates were obtained from soil debris associated with tree species not previously reported as hosts from sites near residences of infected patients. These isolates are fertile under laboratory conditions, produce abundant spores, and are part of both locally and more distantly recombining populations. MLST and whole genome sequence analysis provide compelling evidence that these environmental isolates are the source of human infections. Isolates displayed wide-ranging virulence in macrophage and animal models. When clinical and environmental isolates with indistinguishable MLST profiles were compared, environmental isolates were less virulent. Taken together, our studies reveal an environmental source and risk of C. gattii to HIV/AIDS patients with implications for the >1,000,000 cryptococcal infections occurring annually for which the causative isolate is rarely assigned species status. Thus, the C. gattii global health burden could be more substantial than currently appreciated.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Springer
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: R Blake
authors.initials: RB
authors.lastname: Billmyre
authors.affiliation: David Geffen School of Medicine at UCLA, Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles, California, United States of America.
authors.forename: Elan E
authors.initials: EE
authors.lastname: Filler
authors.affiliation: Institute of Microbiology & Infection and the School of Biosciences, University of Birmingham, Birmingham, United Kingdom; National Institute of Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Voelz
authors.affiliation: Institute of Microbiology & Infection and the School of Biosciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Rhiannon
authors.initials: R
authors.lastname: Pursall
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Piotr A
authors.initials: PA
authors.lastname: Mieczkowski
authors.affiliation: Division of Infectious Diseases, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Larsen
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Fred S
authors.initials: FS
authors.lastname: Dietrich
authors.affiliation: Institute of Microbiology & Infection and the School of Biosciences, University of Birmingham, Birmingham, United Kingdom; National Institute of Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors.forename: Robin C
authors.initials: RC
authors.lastname: May
authors.affiliation: David Geffen School of Medicine at UCLA, Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles, California, United States of America.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Filler
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America; Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Joseph
authors.initials: J
authors.lastname: Heitman
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000382:microbiology; D000818:Animals; D002140:California; D002469:Cell Separation; D003453:Cryptococcosis / Q000235:genetics / Q000382:microbiology*; D056285:Cryptococcus gattii / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000382:microbiology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012988:Soil Microbiology; D014197:Trees / Q000382:microbiology*