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

Abstract

Coccidioides immitis and C. posadasii are two highly pathogenic dimorphic fungal species that are endemic in the arid areas of the new world, including the region from west Texas to southern and central California in the USA that cause coccidioidomycosis (also known as Valley Fever). In highly endemic regions such as southern Arizona, up to 50% of long term residents have been infected. New information about fungal population genetics, ecology, epidemiology, and host-pathogen interactions is becoming available. However, our understanding of some aspects of coccidioidomycosis is still incomplete, including the extent of genetic variability of the fungus, the genes involved in virulence, and how the changes in gene expression during the organism's dimorphic life cycle are related to the transformation from a free-living mold to a parasitic spherule. Unfortunately, efforts to develop an effective subunit vaccine have not yet been productive, although two potential live fungus vaccines have been developed.

Keywords: Coccidioides; Fungi; coccidioidomycosis; dimorphism; genome; immunity; spherule; transcriptome; vaccine.

Figure 1.

A phylogenetic tree of dimorphic fungi that are human pathogens. A few close relatives that are not dimorphic primary pathogens are shown for comparison (not highlighted in tan). The Orders are shown to the right of the boxed names. Organisms within each Order are boxed together. The phylogenetic data was obtained using the NCBI taxonomy tool and the tree was constructed using Phylip-3.695.

Figure 2.

Mycelia containing arthroconidia and a mature spherule with endospores. (a) Mature mycelia grown in vitro showing darkly stained arthroconidia alternating with a nucleate thin walled segments within mycelia (lacto-phenol cotton blue stain). (b) A spherule containing endospores in tissue (Periodic Acid Schiff (PAS)). The images were obtained from the CDC (http://phil.cdc.gov/phil/details.asp). This figure was previously published in the Journal of Fungi [70].

Figure 3.

Numbers of genes upregulated in spherules of three different maturities. Venn diagram of C. immitis genes up-regulated more than 2-fold compared to mycelial gene expression. (a) The data for day 4 spherules are from [41] and (b) the data for Day 2 and day 8 spherules are from [42].