Molecular evolution of the fungi: human pathogens.

Abstract

The morphological, ecological, and clinical diversity among ascomycete fungi that are pathogenic to humans suggest that the potential for pathogenicity may have arisen multiple times within these higher fungi. We have obtained 18S ribosomal DNA sequences from a diverse group of human pathogenic fungi in order to determine their evolutionary origins. The fungi studied include a skin pathogen that is confined to humans (Trichophyton rubrum) and three systemic, facultative parasites that cause histoplasmosis (Histoplasma capsulatum), blastomycosis (Blastomyces dermatitidis) and coccidioidomycosis (Coccidioides immitis) in humans and other higher animals. Also included in our analysis are representatives of non-pathogenic fungi, as well as two opportunistic pathogens, Pneumocystis carinii and Candida albicans, that cause severe disease in immunocompromised individuals, especially those with AIDS. Two of the fungi we sequenced, T. rubrum and C. immitis, are limited to asexual modes of reproduction and therefore lack the sexual structures that are most useful for evolutionary comparison as well as being essential for classification among the higher fungi. Coccidioides immitis is particularly problematic owing to its contradictory and confusing asexual morphologies, which have caused it to be placed in three fungal classes and the protista. Our analysis shows that the specialized, superficial parasite and the systemic, facultative parasites, including C. immitis, are closely related ascomycetes, which clearly demonstrates the power of molecular characters to compensate for missing or confusing reproductive morphology. Analysis also shows that the opportunistic pathogens are more distantly related, with the likely explanation that pathogenicity has arisen more than once within the Ascomycetes.

Gene expression in human fungal pathogen Coccidioides immitis changes as arthroconidia differentiate into spherules and mature

“…Four of the most downregulated genes were homologs of S. cerevisiae genes involved in sex or meiosis (indicated by an asterisk in Table  2). C. immitis has all the genes required for a sexual cycle [37] and has been shown to recombine in nature [38], but the sexual cycle has never been observed. Six of the downregulated protein kinase genes were homologs of S. cerevisiae genes involved in mitosis (indicated by a double asterisk in Table  2).…”

A TCR Transgenic Mouse Reactive with Multiple Systemic Dimorphic Fungi

“…B. dermatitidis, P. brasiliensis ( and P. lutzii), H. capsulatum and C. immitis (and C. posadasii ) are closely related at the level of 18S ribosomal DNA sequences (28, 29). We recently found that Bd 1807 cells respond to a shared immunodominant antigen in B. dermatitidis and H. capsulatum (1).…”

Fungi and the Rise of Mammals

“…That ecological calamity was accompanied by massive deforestation [16], an event followed by a fungal bloom [17], as the earth became a massive compost. Although one cannot know which spores were present at the time, the likelihood that pathogenic fungi existed at the K-T boundary is enhanced by the finding that the potential for pathogenicity probably arose independently several times in evolution [18].…”