Fantastic yeasts and where to find them: the hidden diversity of dimorphic fungal pathogens

Abstract

Dimorphic fungal pathogens are a significant cause of human disease worldwide. Notably, the dimorphic fungal pathogens within the order Onygenales are considered primary pathogens, causing disease in healthy hosts. Current changes in taxonomy are underway due to advances in molecular phylogenetics, population genetics, and new emerging dimorphic fungal pathogens causing human disease. In this review, we highlight evolutionary relationships of dimorphic fungal pathogens that cause human disease within the order Onygenales and provide rationale to support increased investment in studies understanding the evolutionary relationships of these pathogens to improve rapid diagnostics, help identify mechanisms of antifungal resistance, understand adaptation to human host, and factors associated with virulence.

Figure 1

Phylogenetic representation of the evolutionary trajectory of the order onygenales. The branch distribution is based on MLST tree (rPB2, TUB2, TEF3, ITS, and LSU), whole genome phylogentic trees, and node calibrations previously published (4200 core genes) [,^•,71]. Solid black branches are concordant between both phylogenetic studies and dotted branches are due to uncertainty regarding the true phylogenomic position of Emmonsiellopsis. The solid grey branch represents the outgroup formed by Eurotiales species. The solid red square represents the most common ancestor of Onygenales that emerged around 150 MYA and black ellipsis are nodes distinguishing each lineage. Red nodes represent the age of divergence of each species complex previously analyzed [6,12,37,64]. Blastomyces parvus (*) and Emergomyces pasteurianus (#) were previously known as Emmonsia crescens and E. pasteuriana, respectively. The forms of pathogenic structures among the Onygenales are displayed along the tree.

Figure 2

Morphological shifts of Onygenalean fungi. The simple cartoons for each dimorphic Onygenales are shown. In the environment, each of these species is in its hyphal/mycelial form with oval or circular shapes representing the vegetative conidia. In the case of Blastomyces, Emergomyces, Histoplasma, and Paracoccidioides in the host, these switch to yeast-phase with some characteristic differences. Blastomyces yeast cells display a broad bud neck; Emergomyces have yeast cells with unipolar or bipolar budding at narrow base; Paracoccidioides have yeast that can be multibudded. In the host, Coccidioides switches to endosporulating spherules which then ruptures to release endospores. Emmonsia switches to an adiaspore (non-endosporulating spherule). (Illustration created with BioRender).

Figure 3

Estimated global distribution of Onygenales that cause human disease. These geographical locations for endemic sites of Onygenales are an estimate. Histoplasmosis has a worldwide distribution and the map depicts known endemic regions. This map has been adapted from Ref. [, CDC; https://www.cdc.gov/features/fungalinfections/] with distribution of infections caused by Emergomyces () and Blastomyces () adapted from Ref. [53]. (Illustration created with BioRender).