Phylogenetic Analysis Reveals a Cryptic Species Blastomyces gilchristii, sp. nov. within the Human Pathogenic Fungus Blastomyces dermatitidis

Abstract

BackgroundAnalysis of the population genetic structure of microbial species is of fundamental importance to many scientific disciplines because it can identify cryptic species, reveal reproductive mode, and elucidate processes that contribute to pathogen evolution. Here, we examined the population genetic structure and geographic differentiation of the sexual, dimorphic fungus Blastomyces dermatitidis, the causative agent of blastomycosis.Methodology/Principal FindingsCriteria for Genealogical Concordance Phylogenetic Species Recognition (GCPSR) applied to seven nuclear loci (arf6, chs2, drk1, fads, pyrF, tub1, and its-2) from 78 clinical and environmental isolates identified two previously unrecognized phylogenetic species. Four of seven single gene phylogenies examined (chs2, drk1, pyrF, and its-2) supported the separation of Phylogenetic Species 1 (PS1) and Phylogenetic Species 2 (PS2) which were also well differentiated in the concatenated chs2-drk1-fads-pyrF-tub1-arf6-its2 genealogy with all isolates falling into one of two evolutionarily independent lineages. Phylogenetic species were genetically distinct with interspecific divergence 4-fold greater than intraspecific divergence and a high Fst value (0.772, P<0.001) indicative of restricted gene flow between PS1 and PS2. Whereas panmixia expected of a single freely recombining population was not observed, recombination was detected when PS1 and PS2 were assessed separately, suggesting reproductive isolation. Random mating among PS1 isolates, which were distributed across North America, was only detected after partitioning isolates into six geographic regions. The PS2 population, found predominantly in the hyper-endemic regions of northwestern Ontario, Wisconsin, and Minnesota, contained a substantial clonal component with random mating detected only among unique genotypes in the population.Conclusions/SignificanceThese analyses provide evidence for a genetically divergent clade within Blastomyces dermatitidis, which we use to describe a novel species, Blastomyces gilchristii sp. nov. In addition, we discuss the value of population genetic and phylogenetic analyses as a foundation for disease surveillance, understanding pathogen evolution, and discerning phenotypic differences between phylogenetic species.

Name Changes for Fungi of Medical Importance, 2012 to 2015

“…It is also notable for two new cryptic species detected among the dimorphic endemic pathogens Blastomyces dermatitidis and Paracoccidioides brasiliensis. Blastomyces gilchristii and Paracoccidioides lutzii are genetically distinct and taxonomically valid but lack distinct morphological characteristics that allow them to be distinguished during routine laboratory testing (3,4). It is unclear at present whether detection of these particular cryptic species contributes to patient management.…”

Development of a Highly Sensitive and Specific Blastomycosis Antibody Enzyme Immunoassay Using Blastomyces dermatitidis Surface Protein BAD-1

“…Second, the BAD-1 antigen may not contain epitopes recognized by the antibodies produced in some patient samples. This could be associated with the genetic variability of B. dermatitidis, which has recently been described (21)(22)(23). Third, anti-BAD-1 antibodies may be complexed with antigens in the specimen and therefore not free for detection in our assay.…”

Geodemographic Features of Human Blastomycosis in Eastern Wisconsin

“…1 Disease is acquired from the environment by inhalation of spores of the etiologic fungi Blastomyces dermatitdis or Blastomyces gilchristii. 2 Blastomycosis incidence rates are particularly high in Wisconsin compared to the rest of the nation. 3 While reports are emerging from lesser endemic portions of the state, 4,5 most epidemiologic investigations of sporadic and outbreak cases have focused on rural northern and central Wisconsin.…”