INTRODUCTION TO PATHOGENIC FUNGI

Fungi are a subgroup of the Supergroup Opisthokonta (Adl et al. 2005) and com­prise a Kingdom of eukaryotic organisms distinguished by their unique cellular struc­tures (Alexopoulos et al.

Although most parts of a fungus are poten­tially capable of growth, the hyphae constitut­ing the body (thallus) of the fungus typically elongate by apical growth (Alexopoulos et al. 1996). Each partition in a fungal hypha is called a septum. While most fungi produce myce- lia, the network of branched septated hyphae, some exist as single-celled yeasts that reproduce quickly by budding or fission (Alexopoulos et al. 1996). Species that have the capacity to both produce mycelia and live as single cells are dimorphic; dimorphism is common among species that cause diseases in animals (Alexopoulos et al. 1996).

All fungi can reproduce by asexual (somatic) reproduction, and most are known to reproduce sexually. The most common method of asexual reproduction is the production of mitotic spores, with each spore germinating and forming hyphae that then form mycelia. Some fungal spores are produced and borne in sporangia, sac-like structures whose entire contents are converted through cleavage into one or many spores; such spores are called sporangiospores. In contrast, spores produced at the tips or sides of hyphae are called conidia. Most spores are non-motile; how­ever, those of the Phylum Chytridiomycota have a flagellum and are called zoospores (Alexopoulos et al.

Sexual reproduction involves the union of two compatible nuclei and usually results in the for­mation of specialized spores, including oospores, zygospores, ascospores, and basidiospores (Alexopoulos et al. 1996). Sexual stages have not been described for some species of fungi or have been lost, especially among ascomycetes and basidiomycetes. The term teleomorph is used to identify a meiotic sexual form that produces ascospores or basidiospores; the term anamorph refers to a mitotic asexual form that does not pro­duce spores (Alexopoulos et al. 1996).

Fungi undergoing sexual reproduction fall into one of three morphological categories (Alexopoulos et al. 1996). Most fungi are sexu­ally undifferentiated, and sexually functional structures are produced that are morphologically indistinguishable as male or female. In contrast, monoecious (hermaphroditic) fungi have thalli that each bear both male and female organs that may (or may not) be compatible. Rarely, there are dioecious fungi in which some thalli bear only male and some bear only female organs.

Asexual reproduction is important for rap­idly colonizing a new habitat because it results in the production of a large number of indi­viduals in a short time. Sexual reproduction results in a high incidence of recombination and formation of new genotypes that enable the fungi to adapt more readily to new condi­tions (Alexopoulos et al. 1996). Overall, fungi are very successful organisms, as evidenced by their ubiquity in nature; they function primar­ily as decomposers and saprophytes, and less commonly as parasites of living hosts.

Fungal Systematics

Although once classified with plants, the emer­gence of molecular phylogenetics as a discipline has made it clear that fungi are more closely related to animals (Adl et al.

There is a proposal for a major revision of the phylogenetic classification of the Kingdom Fungi that calls for one subkingdom, Dikarya, compris­ing the Ascomycetes and Basidiomycetes, as well as seven phyla (Hibbett et al. 2007). However, until it is clear where the majority of pathogenic fungi are placed in this revision, we currently fol­low the more traditional format of recognizing four phyla in the Kingdom Fungi: Chytridiomy- cota, Zygomycota, Ascomycota, and Basidiomy- cota (App. 1: Table 6).

The Form-group Deuteromycota (App. 1: Table 6), also called Mitosporic Fungi (Howard 2003), was established by taxonomists to include organisms known only in anamorph form. In recent years, molecular phylogeny has been applied extensively to members of the Kingdom Fungi (Lutzoni et al. 2004, James et al. 2006, Spatafora et al. 2006), and many asexual fungi have been linked with their sexual relatives. For example, members of the pathogenic genera Blastomyces, Emmonsia, Histoplasma, and Paracoccidioides are closely related, with about 5% base differences, and with even less of a difference between Blastomyces and Emmonsia (Gueho et al. 1997). All now are known to be closely allied with other mem­bers of the Family Onygenaceae in the Class Ascomycetes (Howard 2003). In this text, mem­bers of the Deuteromycota are included with their close sexual relatives wherever possible.

The Phylum Chytridiomycota comprises those members of the Kingdom Fungi that produce motile cells in their life cycles (Alexopoulos et al. 1996). These flagellated spores (zoospores) are produced in four of the five orders within the single Class Chytrid- iomycetes (Alexopoulos et al. 1996) and are homologous to the non-fungal opisthokonts (App. 1) (Barr 1992). Current evidence is that the Chytridiomycota are polyphyletic, consisting of some early diverging lineages that retained the zoospore (James et al. 2006). However, the euchytrids, a large clade of orders within the Chytridiomycota, appear to be monophyletic (James et al. 2006).

The Phylum Zygomycota contains those fungi that produce zygospores, formed from morphologically identical gametes, as a result of sexual reproduction (Howard 2003). Current evidence is that the Zygomycota also are poly- phyletic (James et al. 2006). All representatives of the Class Trichomycetes are obligate para­sites of arthropods and will not be addressed further. The Class Zygomycetes has two orders, Mucorales and Entomophthorales, both of which include important animal pathogens. The Mucorales generally produce nonseptate hyphae, while the Entomophthorales usually have septated hyphae (Howard 2003).

The Phylum Ascomycota comprises fungi that reproduce sexually by means of ascospores that are contained in a specialized sac called an ascus (Howard 2003). Molecular phylogeny studies have allowed associations of many former mem­bers of the Deuteromycota to be classified, even when known teleomorphs were not identified for the specific anamorph forms (Lutzoni et al. 2004); these are included when applicable. Two classes commonly are recognized. The Endomycetes undergo asexual reproduction by budding or fis­sion of somatic cells, whereas Ascomycetes form blastic or thallic conidia (Howard 2003). Current genetic phylogeny of the Kingdom Fungi sup­ports the monophyly of the Ascomycota (James et al. 2006).

Members of the Phylum Basidiomycota all produce spores (basidiospores) on the outside of a club-shaped to elongate structure (basid­ium).

Fungal Identification

Laboratory identification of mycoses calls for the initial collection and storage of specimens and the proper identification, which generally is based on direct microscopic examination to determine size and morphology, antigenic detection, finding fungus-specific metabolites, detection of cell wall components, detection of fungus-specific nucleic acids, and direct cultur­ing on fungal media (Merz and Roberts 1999). Direct examination of fungi within clinical specimens can be done with potassium hydrox­ide, India ink, or calcofluor white, as well as Giemsa and a few other staining techniques (Kwon-Chung and Bennett 1992). A variety of media are used for culturing fungi from clinical specimens, and there are a number of laboratory techniques for their identifica­tion (Kwon-Chung and Bennett 1992). Many of these are similar to techniques used for the cultivation and identification of pathogenic bacteria (Gough 1997).

Fungal Diseases

While the number of fungi pathogenic to vertebrates and invertebrates is not certain, it probably is not high. For example, of the esti­mated 250,000 species (Dixon et al. 1999) to 1.5 million species (Hawksworth 1991) of fungi known, only about 120 species pathogenic to humans are known (McGinnis et al. 1999).

Rarely, fungi are contagious; examples include epidermal parasites such as Pseu- dogymnoascus (Geomyces) destructans (cause of white-nose syndrome in bats) and Candida albi­cans, a systemic parasite. But most pathogenic fungi are primarily free-living saprophytes that do not require an animal host for survival or propagation (Hogan et al. 1996); they are opportunists of low virulence that only rarely cause disease in healthy individuals.

It is not clear why there is a selective pressure for continued animal pathogenicity among fungi well adapted to abiotic environments. However, soil amebae may ingest the yeast forms of some soil fungi and help select and maintain traits that confer virulence in these pathogenic fungi for mammals (Steenbergen et al. 2004).

Fungi cause several types of diseases. The most common type of fungal disease is a myco­sis, the direct growth of fungi on or in host cells. Pathogenic fungi have varied growth patterns on or in their hosts, and often are labeled as superficial, cutaneous, subcutaneous, or systemic (Friend 1999b). In contrast, a mycotoxicosis is a disease resulting from fungal metabolites acquired through ingestion, inhalation, or abra­sion (Bennett and Klich 2003). Allergic diseases may result from fungal spores or colonies developing in the lungs.