Thermally Dimorphic Human Fungal Pathogens--Polyphyletic Pathogens with a Convergent Pathogenicity Trait

Abstract

Fungi are adept at changing their cell shape and developmental program in response to signals in their surroundings. Here we focus on a group of evolutionarily related fungal pathogens of humans known as the thermally dimorphic fungi. These organisms grow in a hyphal form in the environment but shift their morphology drastically within a mammalian host. Temperature is one of the main host signals that initiates their conversion to the "host" form and is sufficient in the laboratory to trigger establishment of this host-adapted developmental program. Here we discuss the major human pathogens in this group, which are Blastomyces dermatiditis, Coccidioides immitis/posadasii, Histoplasma capsulatum, Paracoccidioides brasiliensis/lutzii, Sporothrix schenckii, and Talaromyces marneffei (formerly known as Penicillium marneffei). The majority of these organisms are primary pathogens, with the ability to cause disease in healthy humans who encounter them in endemic areas.

Figure 1.

Simplified schematic of temperature-regulated forms of thermally dimorphic fungal pathogens. Simple cartoons of the environmental and host forms of each fungal species are shown. In the environmental hyphal form of these organisms, oval swellings depict vegetative conidia. In the case of H. capsulatum, tuberculate macroconidia and microconidia are shown. In the case of Coccidioides spp., disarticulating arthroconidia are shown. Some of the characteristic differences between yeast-phase growth are depicted: Blastomyces dermatitidis yeast cells have a broad bud neck, Paracoccidioides yeast can be multibudded, and T. marneffei yeast divides by fission rather than budding. Note that the relative scale of different cell types (within and between species) is not meant to be accurate. (Illustration provided by Davina Hocking Murray.)

Figure 2.

Molecular phylogenetic analysis of dimorphic fungal pathogens. The evolutionary tree is based on a protein comparison from the major dimorphic human pathogens and includes a number of other fungal pathogens for reference. Human pathogens (red typeface), plant pathogens (green typeface), and nonpathogens (black typeface) are shown and marked as true dimorphic species with free-living vegetative cell types (blue circle) and species with morphological transitions that are not free-living vegetative cell types (blue triangle). With the exception of C. neoformans and U. maydis, which are in the phylum Basidiomycota, all of the other species are in the phylum Ascomycota. These species cover a diverse range of orders (Onygenales, green; Eurotiales, yellow; Ophiostomales, orange; Magnaporthales, brown; and Saccharomycetales, red). To generate the phylogenetic relationships between organisms, the Pfam domain Gcd10p was used to identify Gcd10 sequences from the 16 species of interest. CLUSTALX 2.1 (Larkin et al. 2007) was used to align the full-length protein sequences and generate a bootstrapped neighbor-joining tree (1000 bootstraps; all internal nodes had a bootstrap value of at least 700). (Mark Voorhies contributed to this analysis.)