Phylogenetic analysis of 11 genetic loci and results from many genotyping studies revealed significant genetic diversity with the pathogenic Cryptococcus gattii/Cryptococcus neoformans species complex. Genealogical concordance, coalescence-based, and species tree approaches supported the presence of distinct and concordant lineages within the complex. Consequently, we propose to recognize the current C. neoformans var. grubii and C. neoformans var. neoformans as separate species, and five species within C. gattii. The type strain of C. neoformans CBS132 represents a serotype AD hybrid and is replaced. The newly delimited species differ in aspects of pathogenicity, prevalence for patient groups, as well as biochemical and physiological aspects, such as susceptibility to antifungals. MALDI-TOF mass spectrometry readily distinguishes the newly recognized species.

In 1999, the population of Vancouver Island, Canada, began to experience an outbreak of a fatal fungal disease caused by a highly virulent lineage of Cryptococcus gattii. This organism has recently spread to the Canadian mainland and Pacific Northwest, but the molecular cause of the outbreak remains unknown. Here we show that the Vancouver Island outbreak (VIO) isolates have dramatically increased their ability to replicate within macrophages of the mammalian immune system in comparison with other C. gattii strains. We further demonstrate that such enhanced intracellular parasitism is directly linked to virulence in a murine model of cryptococcosis, suggesting that this phenotype may be the cause of the outbreak. Finally, microarray studies on 24 C. gattii strains reveals that the hypervirulence of the VIO isolates is characterized by the up-regulation of a large group of genes, many of which are encoded by mitochondrial genome or associated with mitochondrial activities. This expression profile correlates with an unusual mitochondrial morphology exhibited by the VIO strains after phagocytosis. Our data thus demonstrate that the intracellular parasitism of macrophages is a key driver of a human disease outbreak, a finding that has significant implications for a wide range of other human pathogens.cryptococcus ͉ macrophage ͉ Vancouver Island outbreak ͉ virulence

Trichosporon asahii (Trichosporon beigelii) infections are rare but have been associated with a wide spectrum of clinical manifestations, ranging from superficial involvement in immunocompetent individuals to severe systemic disease in immunocompromised patients. We report on the recent recovery of T. asahii isolates with reduced susceptibility in vitro to amphotericin B (AMB), flucytosine, and azoles from six nongranulocytopenic patients who exhibited risk factors and who developed either superficial infections (four individuals) or invasive infections (two individuals) while in intensive care units. The latter two patients responded clinically and microbiologically to AMB treatment. All six isolates were closely related according to random amplified polymorphic DNA studies and showed 71% similarity by amplified fragment length polymorphism analysis, suggesting a common nosocomial origin. We also review the literature pertaining to T. asahii infections and discuss the salient characteristics of this fungus and recent taxonomic proposals for the genus.Trichosporon infections are associated with a wide spectrum of clinical manifestations, ranging from superficial cutaneous involvement in immunocompetent individuals to severe systemic disease in immunocompromised patients (9, 44). Trichosporon asahii (Trichosporon beigelii) has increasingly been described as an opportunistic pathogen involved in disseminated infections in patients with profound granulocytopenia (9,11,26). Less commonly reported risk factors associated with infections caused by this agent include treatment with immunosuppressive drugs, transplantation, AIDS, extensive burns, and the presence of implanted prosthetic devices (9,11,14,20,24,27,29).Trichosporon species were the most common non-Candida cause of fungemia at a national cancer institute (23). Disseminated Trichosporon infections in immunocompromised patients are frequently fatal, despite therapy with amphotericin B (AMB) (9,44,46). This antifungal agent has been shown to have a limited in vitro effect against Trichosporon species. In contrast, azoles have been demonstrated to have in vitro activity against members of this genus and their use has been associated with favorable responses in animal models (2,3,9,27,31,32,45,46).We report on the recent recovery of T. asahii isolates resistant in vitro to AMB and azoles from six nongranulocytopenic patients who developed either invasive or superficial infections while hospitalized in different intensive care units (ICUs). We describe the demographic and major clinical characteristics of these patients and review the literature pertaining to T. asahii infections. Results from molecular biology-based studies based on random amplified polymorphic DNA (RAPD) and amplified fragment length polymorphism (AFLP) analyses suggest that the isolates recovered from specimens of these six patients were closely related. In addition, we discuss the salient characteristics of this fungus and recent taxonomic proposals for the genus. MATERIALS AND METHODSCase re...

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