title: Phenotypic differences of Cryptococcus molecular types and their implications for virulence in a Drosophila model of infection.
abstract: Compared to Cryptococcus neoformans, little is known about the virulence of the molecular types in Cryptococcus gattii. We compared in vitro virulence factor production and survival data using a Drosophila model of infection to further characterize the phenotypic features of different cryptococcal molecular types. Forty-nine different isolates were inoculated into wild-type flies and followed for survival. In vitro, isolates were assessed for growth at 30 and 37°C, melanin production, capsule size, resistance to H(2)O(2), and antifungal susceptibility. A mediator model was used to assess molecular type and virulence characteristics as predictors of survival in the fly model. VGIII was the most virulent molecular type in flies (P < 0.001). At 30°C, VGIII isolates grew most rapidly; at 37°C, VNI isolates grew best. C. gattii capsules were larger than those of C. neoformans (P < 0.001). Mediator model analysis found a strong correlation of Drosophila survival with molecular type and with growth at 30°C. We found molecular-type-specific differences in C. gattii in growth at different temperatures, melanin production, capsule size, ability to resist hydrogen peroxide, and antifungal susceptibility, while growth at 30°C and the VGIII molecular type were strongly associated with virulence in a Drosophila model of infection.
authors.affiliation: Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California, USA Department of Internal Medicine, Division of Infectious Diseases, University of California, Davis, Davis, California, USA grthompson@ucdavis.edu dkontoyi@mdanderson.org.
authors.forename: George R
authors.initials: GR
authors.lastname: Thompson
authors.affiliation: Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Albert
authors.affiliation: Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Hodge
authors.affiliation: Department of Public Health Sciences, Division of Biostatistics, University of California, Davis, Davis, California, USA.
authors.forename: Machelle D
authors.initials: MD
authors.lastname: Wilson
authors.affiliation: Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Sykes
authors.affiliation: Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California, USA.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Bays
authors.affiliation: Molecular Mycology Research Laboratory, Centre for Infectious Diseases and Microbiology, Sydney Medical School, Marie Bashir Institute for Infectious Diseases and Microbiology, The University of Sydney, New South Wales, Australia.
authors.forename: Carolina
authors.initials: C
authors.lastname: Firacative
authors.affiliation: Molecular Mycology Research Laboratory, Centre for Infectious Diseases and Microbiology, Sydney Medical School, Marie Bashir Institute for Infectious Diseases and Microbiology, The University of Sydney, New South Wales, Australia.
authors.forename: Wieland
authors.initials: W
authors.lastname: Meyer
authors.affiliation: Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA grthompson@ucdavis.edu dkontoyi@mdanderson.org.
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use; D056285:Cryptococcus gattii / Q000166:cytology / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D004331:Drosophila melanogaster / Q000382:microbiology*; D025141:Drug Resistance, Fungal; D015964:Gene Expression Regulation, Bacterial; D008543:Melanins / Q000378:metabolism; D014774:Virulence
chemical_list: D000935:Antifungal Agents; D008543:Melanins