Dust Devil: The Life and Times of the Fungus That Causes Valley Fever

Coccidioides immitis and C. posadasii are pathogenic, dimorphic, soil-dwelling Ascomycetes in the Onygenales order. On average, both Coccidioides species have 29 Mb haploid genomes, containing approximately 10,000 open reading frames (ORFs) on five chromosomes [1]. Coccidioides’most recent common ancestor underwent gene family expansions for proteases and keratinases, membrane biology genes, and toxin production, all likely utilized for survival in animal tissues and morphological changes; and a loss of genes associated with degradation of plant tissue, such as tannases, cellulases, and cutinases [1]. Coccidioides and other fungi in the family Onygenaceae are able to degrade keratin and may cause skin disease in humans and animals. Both species of Coccidioides are distantly related to other dimorphic human pathogens, such as Histoplasma (Ajellomyces) capusulatum, in the new family Ajellomycetaceae [2]. Both Coccidioides species have similar biology, with a well-characterized asexual life cycle with distinct saprobic and parasitic stages, and only molecular evidence of a sexual cycle (Fig 1). In the saprobic phase, Coccidioides cycles between mycelial and arthroconidial stages. Arthroconidia are abscised and become airborne by soil disturbance. Inhalation of arthroconidia by a potential host can lead to coccidioidomycosis, commonly known as (San Joaquin) Valley fever. In an infected host, Coccidioides cycles between uninucleate endospores and multinucleate spherules (Fig 1). Differential phenotypes between the species, including temperature sensitivity and salt tolerance, have been described [3] (personal communication, Marc Orbach to B. Barker). No differential disease phenotypes have been investigated, although extreme variation in virulence among strains is documented [4]. The most pathogenic strains can cause fatal disease within eight days with as few as 50 arthroconidia administered intranasally in immunocompetent mice, and some cause much later onset of disease symptoms and death [4–6]. For humans, minimum dosage is not known, but it has been stated that the infectious dose is a single arthroconidium [7]. Both species have been shown to infect a wide variety of mammals, with varying levels of disease [8]. Molecular evidence of mating includes identification and characterization of mating type loci, recombination, and distinct gene genealogies [9–11]. In addition to intra-species sexual recombination, population genomics revealed signatures of hybridization and gene introgression between the two species [12]. At this time, no laboratory-controlled genetic recombination or sexual structures have been described.