Phylogenetics and Population Structure
There are two distinct cryptic species within the genus Coccidioides (Ascomycota, Pezizomycotina, Eurotiomycetes, Onygenales, Onygenaceae): Coccidioides immitis and C. posadasii (Fisher et al.
2002). Previous phylogenetic analyses and morphological characterization showed that Uncinocarpus reesii, a keratinophilic saprotroph, is one of the closest related fungi to Coccidioides (Sigler et al. 1998; Pan et al. 1994). However, recent work reveals that Amauroascus mutatus, A. niger, Byssoonygena ceratinophila, and Chrysosporium queenslandicum are phylogenetically closer to Coccidioides than U. reesii (Whiston and Taylor 2015). Within the Onygenaceae, no other dimorphic human pathogens have been identified; however other animal pathogens exist (Sigler et al. 1998; Herr et al. 2001; Sigler et al. 2013). The Ajellomycetaceae, which are distinct from the Onygenaceae, include Blastomyces dermatitidis, Histoplasma capsulatum, Paracoccidioides brasiliensis (Untereiner et al. 2004), and Emergomyces species (Dukik et al. 2017).The Onygenales contain at least these two families as well as the Gymnoascaceae and Arthrodermataceae, but these are still preliminary assignments, and more work remains to be done to understand the complete picture of phylogenetic relationships. The Onygenales are a sister order to the Eurotiales, and the class containing these orders, the Eurotiomycetes, includes a number of species that cause disease in both animals and plants (Wang et al. 2009). Several genomes of Eurotiomycetes have been sequenced, which allows for comparative genomic studies.
The current understanding of genetic population structure within C. immitis suggests the existence of two populations: San Joaquin/Central Valley California (SJV) and Southern California/Mexico (SDMX) (Fisher et al. 2001, 2002). The genetic population structure of C. posadasii suggests three main populations: Texas/ South America (TXSA), Mexico, and Arizona.
Limited gene flow occurs among populations. More effort to understand genetic diversity in Mexico and Central and South America is needed. Recent evidence for even smaller-scale population structure within Arizona was reported (Teixeira and Barker 2016). Yuma and Phoenix isolates are distinct from Tucson patient and soil isolates, which suggests there may be specific ecological adaptations between these two areas. The Sonoran Desert is a highly variable landscape, which ranges from desert upland/grassland (Tucson) to the lower elevation desert biome (Phoenix/Yuma). Coccidioides growing in the soil in these areas would experience different abiotic and/or biotic stressors (Fisher et al. 2007; Lacy and Swatek 1974).Additionally, genetic diversity in environmental and veterinary isolates differs from the genetic diversity among isolates infecting humans (Teixeira and Barker 2016). Human clinical isolates therefore provide valuable insights into population structure; however, isolates obtained directly from the environment are necessary to truly understand fine-scale population structure and determine if certain regions (i.e., Tucson vs. Phoenix) support the growth and survival of specific genotypes. Perhaps more intriguing is that the pool of diversity in the environment is higher than what is observed to cause disease to the human population, even with a small number of isolates available for genetic comparisons. Environmental isolates of Coccidioides exist, but they are difficult to obtain (Barker et al. 2012; Johnson et al. 2014; Litvintseva et al. 2015; Lauer et al. 2012; Brillhante et al. 2012; Baptista-Rosas et al. 2007; Fisher et al. 2007). Greater effort is needed to assess the environmental reservoir of Coccidioides in the environment and true population structure.
The first reported case of the disease was described by Alejandro Posadas over 120 years ago in Argentina (Posadas 1892). Granulomas in skin lesions resembling a protist were observed. In 1896, the organism was named Coccidioides immitis: “Coccidioides” for the suspected coccidium protozoan and “immitis” which is Latin for “not mild” (Rixford and Gilchrist 1896). In 1900, it was clearly shown by researchers working in California that the causative organism was a fungus. Ophuls (1905) named the protozoan-like structure a spherule, a parasitic stage of the life cycle of the fungus. The disease was considered rare and fatal, as these were the first category of cases to be recognized (Morris 1924; Ryfkogel 1908). However, this view was changed by five cases of acute infections from which patients fully recovered and proved that Coccidioides exposure could result in nonlethal illness (Dickson 1937).
4.2