The fungal kingdom includes at least 6 million eukaryotic species and is remarkable with respect to its profound impact on global health, biodiversity, ecology, agriculture, manufacturing, and biomedical research. Approximately 625 fungal species have been reported to infect vertebrates, 200 of which can be human associated, either as commensals and members of our microbiome or as pathogens that cause infectious diseases. These organisms pose a growing threat to human health with the global increase in the incidence of invasive fungal infections, prevalence of fungal allergy, and the evolution of fungal pathogens resistant to some or all current classes of antifungals.

Iron is the most abundant transition metal in the human body and its bioavailability is stringently controlled. In particular, iron is tightly bound to host proteins such as transferrin to maintain homeostasis, to limit potential damage caused by iron toxicity under physiological conditions and to restrict access by pathogens. Therefore, iron acquisition during infection of a human host is a challenge that must be surmounted by every successful pathogenic microorganism. Iron is essential for bacterial and fungal physiological processes such as DNA replication, transcription, metabolism and energy generation via respiration. Hence, pathogenic bacteria and fungi have developed sophisticated strategies to gain access to iron from host sources. Indeed, siderophore production and transport, iron acquisition from heme and host iron-containing proteins such as hemoglobin and transferrin, and reduction of ferric to ferrous iron with subsequent transport are all strategies found in bacterial and fungal pathogens of humans. This review focuses on a comparison of these strategies between bacterial and fungal pathogens in the context of virulence and the iron limitation that occurs in the human body as a mechanism of innate nutritional defence.

▪ Abstract Mating type genes regulate sexual compatibility and sexual reproduction in fungi. This review focuses on recent molecular analyses of well-characterized mating systems from representative ascomycete (Neurospora crassa, Podospora anserina) and basidiomycete (Ustilago maydis, Coprinus cinereus, Schizophyllum commune) fungi. These mating systems include many conserved components, such as gene regulatory polypeptides and pheromone/receptor signal transduction cascades, as well as conserved processes, like self-nonself recognition and controlled nuclear migration. The components' structures and their genetic arrangements in the mating system vary greatly in different fungi. Although similar components and processes are also found in ascomycete yeasts (Saccharomyces cerevisiae and Schizosaccharomyces pombe), the filamentous systems exhibit properties not encountered in yeast. Mating type genes act within, and control the development of, spatially differentiated fruiting bodies. The complex mating systems of basidiomycetes, unlike ascomycete systems, involve novel one-to-many specificity in both pheromone-receptor and homeodomain protein interactions.

Cryptococcus gattii, emergent on Vancouver Island, British Columbia (BC), Canada, in 1999, was detected during 2003–2005 in 3 persons and 8 animals that did not travel to Vancouver Island during the incubation period; positive environmental samples were detected in areas outside Vancouver Island. All clinical and environmental isolates found in BC were genotypically consistent with Vancouver Island strains. In addition, local acquisition was detected in 3 cats in Washington and 2 persons in Oregon. The molecular profiles of Oregon isolates differed from those found in BC and Washington. Although some microclimates of the Pacific Northwest are similar to those on Vancouver Island, C. gattii concentrations in off-island environments were typically lower, and human cases without Vancouver Island contact have not continued to occur. This suggests that C. gattii may not be permanently colonized in off-island locations.

Cryptococcus gattii recently emerged as the causative agent of cryptococcosis in healthy individuals in western North America, despite previous characterization of the fungus as a pathogen in tropical or subtropical regions. As a foundation to study the genetics of virulence in this pathogen, we sequenced the genomes of a strain (WM276) representing the predominant global molecular type (VGI) and a clinical strain (R265) of the major genotype (VGIIa) causing disease in North America. We compared these C. gattii genomes with each other and with the genomes of representative strains of the two varieties of Cryptococcus neoformans that generally cause disease in immunocompromised people. Our comparisons included chromosome alignments, analysis of gene content and gene family evolution, and comparative genome hybridization (CGH). These studies revealed that the genomes of the two representative C. gattii strains (genotypes VGI and VGIIa) are colinear for the majority of chromosomes, with some minor rearrangements. However, multiortholog phylogenetic analysis and an evaluation of gene/sequence conservation support the existence of speciation within the C. gattii complex. More extensive chromosome rearrangements were observed upon comparison of the C. gattii and the C. neoformans genomes. Finally, CGH revealed considerable variation in clinical and environmental isolates as well as changes in chromosome copy numbers in C. gattii isolates displaying fluconazole heteroresistance. IMPORTANCE Isolates of Cryptococcus gattii are currently causing an outbreak of cryptococcosis in western North America, and most of the cases occurred in the absence of coinfection with HIV. This pattern is therefore in stark contrast to the current global burden of one million annual cases of cryptococcosis, caused by the related species Cryptococcus neoformans , in the HIV/AIDS population. The genome sequences of two outbreak-associated major genotypes of C. gattii reported here provide insights into genome variation within and between cryptococcal species. These sequences also provide a resource to further evaluate the epidemiology of cryptococcal disease and to evaluate the role of pathogen genes in the differential interactions of C. gattii and C. neoformans with immunocompromised and immunocompetent hosts.