Genomics of Pathogenic Fungi

Gerwald A. Köhler, Alan Kuo, George Newport, and Nina Agabian 18.1


Fungi are eukaryotic microorganisms with typical nuclear membranes, but with several features that distinguish them from plants, animals, and protozoa. Like plants they contain cell walls and are with very few exceptions nonmotile; however, they lack chlorophyll. Fungi can be unicellular or multicellular to filamentous forms with sexual and/or asexual propagation. The existence of these two modes of reproduction has led to a dual nomenclature for many species, because sexual states (teleomorphs) often develop under different conditions with different morphology than their asexual counterparts (anamorphs). For example, Emericella nidulans is the teleomorph of the well-known and biotechnologically important anamorph Aspergillus nidulans. For many fungi, including some of the most important pathogenic species, the teleomorphic states are unknown or have been lost during evolution. Deuteromycota is a nonphylogenetic form phylum into which these "Fungi Imperfecti" are classified, the majority of them being anamorphs of ascomycetous fungi. In general, fungi have been classified according to morphological criteria, a phenotypic approach that still has its merits in the clinical setting. Recently, cladistic and molecular methods like sequence determination of ribosomal RNA genes or other phylogenetic markers have addressed some ambiguities in fungal phylogeny, especially in the gray zone between protozoa and fungi. For instance, molecular phylogenetic studies have brought the major opportunistic pathogen Pneumocystis carinii, formerly regarded as a protozoan, into the fungal phylum Ascomycota [1, 2]. In a similar manner, it was discovered that microsporidia are not protozoa, but rather highly specialized fungi [3].

Among the more than 70000 known fungal species [4] known to date, only about 150 have been associated with infections of humans or animals [5]. However, with the growing number of immunocompromised individuals, new fungal pathogens are emerging steadily; recent estimates indicate a rate of20 species per year [6]. Despite an ever-increasing list of opportunistic pathogens, however, fungal pathogenesis in humans and animals is still a young field of research, and our understanding of fungal pathogenesis is nowhere near our understanding of bacterial pathogenesis. Recent genomics advances, especially completion of the first eukaryotic genome sequence from the fungus Saccharomyces cerevisiae in 1996 [7] and the first genome sequence of a pathogenic fungus, Candida albicans in 2004 [8], will help us to study the intricate relationship of fungi with their higher eukar-yotic relatives. The following review summarizes the current status of fungal genomics, focusing on the most important human pathogens.

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