Comparative genomic analyses of the human fungal pathogens Coccidioides and their relatives

Abstract

While most Ascomycetes tend to associate principally with plants, the dimorphic fungi Coccidioides immitis and Coccidioides posadasii are primary pathogens of immunocompetent mammals, including humans. Infection results from environmental exposure to Coccidiodies, which is believed to grow as a soil saprophyte in arid deserts. To investigate hypotheses about the life history and evolution of Coccidioides, the genomes of several Onygenales, including C. immitis and C. posadasii; a close, nonpathogenic relative, Uncinocarpus reesii; and a more diverged pathogenic fungus, Histoplasma capsulatum, were sequenced and compared with those of 13 more distantly related Ascomycetes. This analysis identified increases and decreases in gene family size associated with a host/substrate shift from plants to animals in the Onygenales. In addition, comparison among Onygenales genomes revealed evolutionary changes in Coccidioides that may underlie its infectious phenotype, the identification of which may facilitate improved treatment and prevention of coccidioidomycosis. Overall, the results suggest that Coccidioides species are not soil saprophytes, but that they have evolved to remain associated with their dead animal hosts in soil, and that Coccidioides metabolism genes, membrane-related proteins, and putatively antigenic compounds have evolved in response to interaction with an animal host.

Coccidioides immitis and posadasii; A review of their biology, genomics, pathogenesis, and host immunity

“…Coccidioides species are fungi within Ascomycete division, Eurotiomycetes class, Onygenales order [2,3]. This order includes a variety of dimorphic human pathogens capable of causing invasive disease in immunologically normal hosts, including Histoplasma capsulatum, Paracoccidioides spp., and Blastomyces spp.…”

“…Several non-pathogenic but closely related species are also found within this order (Figure 1). Coccidioides immitis and C. posadasii are morphologically identical and their predicted proteins are more than 90% homologous [2]. They cannot be distinguished by serologic tests, but the two species can be distinguished by genetic polymorphisms, and some differences in growth characteristics have been reported [4,5].…”

“…At least four chromosomes have been identified by contour-clamped homogeneous electric field gel electrophoresis [36]. The genomes are haploid and no mating has been observed within or between species, although genes coding for mating functions are present [2] and genetic recombination occurs [35]. About 18% of the genome consists of repetitive DNA.…”

Call for a California Coccidioidomycosis Consortium to Face the Top Ten Challenges Posed by a Recalcitrant Regional Disease

“…Interestingly, comparative genomics has shown that Coccidioides species lack genes for several enzymes widely used by fungi to digest plant cell walls, but they have expanded gene families of enzymes that digest animal protein [27]. These data suggest that Coccidioides may not be primarily saprophytic in soil, but saprozoic in the carcasses of animals infected with Coccidioides spp.…”

“…These data suggest that Coccidioides may not be primarily saprophytic in soil, but saprozoic in the carcasses of animals infected with Coccidioides spp. when the animals were alive [23,27]. Thus, it may be possible to assess the hazard of humans contracting coccidioidomycosis in a particular geographic area by surveying Perognathus and Dipodomys species for the presence of Coccidioides species either by necropsies with culture directly or by doing serology.…”