Fungal Taxonomy and Classification

Fungi form a kingdom within the Opisthokonta, the lineage that also contains animals. This shared ancestry explains the overlap in basic cell biology between fungi and humans, and the narrow selectivity of antifungal drugs.

Classification now rests on molecular phylogeny. Morphology alone groups unrelated fungi that converge on similar forms, such as yeasts, black yeasts and moulds, and separates close relatives that differ in growth form.

Two rules govern naming:

• One fungus, one name: since 2013 a single name applies to each fungus. The old system of separate names for the sexual stage (teleomorph) and asexual stage (anamorph) has been abandoned. Teleomorph names such as Ajellomyces, Arthroderma and Neosartorya persist only in older literature.
• Barcode identification: the internal transcribed spacer (ITS) region of ribosomal DNA is the universal fungal barcode. Sequence data have split many historical species into complexes and cryptic species.

Taxonomic names change frequently. Clinical groupings (yeast, mould, dimorphic fungus, dematiaceous fungus) are more stable than species names and carry the diagnostic and therapeutic information.

The term Zygomycota is obsolete. The older word zygomycosis has been replaced by mucormycosis (Mucorales) and entomophthoromycosis (Basidiobolus, Conidiobolus), because the two groups differ in host, tissue pattern and tempo of disease.

Microsporidia are placed within or at the base of the fungal kingdom. They cause diarrhoea and other disease in advanced HIV, are diagnosed by modified trichrome staining and PCR, and are not managed with the antifungal drugs used for other fungi.

Ascomycota contain most medically important fungi.

Two phylogenetic points explain clinical behaviour in Candida:

• Candida albicans, Candida tropicalis, Candida parapsilosis, Candida dubliniensis and Candida auris lie in the CTG clade, in which the CUG codon encodes serine instead of leucine.
• Candida glabrata and Candida krusei lie outside it. Candida glabrata is more closely related to Saccharomyces cerevisiae than to Candida albicans, which fits its haploid genome and its different azole susceptibility.

Medically important basidiomycetes are yeasts or yeast like fungi: Cryptococcus (Tremellomycetes), Trichosporon (Tremellomycetes), Malassezia (Ustilaginomycotina) and Rhodotorula (Pucciniomycotina). Their shared biochemistry separates them from ascomycetous yeasts in the laboratory.

A positive urease test on a yeast therefore points away from Candida albicans and towards a basidiomycete, which has direct management consequences because the whole group is echinocandin resistant.

Mucorales and Entomophthorales are both traditionally called zygomycetes, but they behave differently.

Disease names built on tissue form complement the phylogenetic scheme and are used in reports and histopathology requests.

Actinomycetoma is clinically identical to eumycetoma but is caused by filamentous bacteria (Nocardia, Actinomadura, Streptomyces). It is not a fungal infection, and the two respond to entirely different therapy.

Dermatophytes are also classified by ecological niche, which predicts the inflammatory response:

Sequence based identification has exposed cryptic species that are morphologically near identical but differ in virulence or drug susceptibility.

• ITS sequencing resolves most yeasts and many moulds.
• Calmodulin or beta tubulin sequencing is needed for Aspergillus section and cryptic species level identification, where ITS has insufficient resolution.
• Translation elongation factor 1 alpha sequencing is the principal locus for Fusarium.
• MALDI TOF mass spectrometry identifies common yeasts and moulds rapidly but depends on database completeness. Rare moulds and cryptic species are frequently unidentified or misassigned.
• Older biochemical yeast identification platforms commonly misidentify Candida auris as Candida haemulonii, Candida duobushaemulonii, Rhodotorula glutinis, Candida sake or Candida famata. This is a recognised route to missed outbreaks.