Diagnostic Mycology: Xtreme Challenges

Abstract

Developing any diagnostic assay that receives United States Food and Drug Administration (FDA) approval can be a slow and difficult process. FDA-approved assays for fungal diagnosis are generally few in number and are focused mainly on diagnosing candidiasis, which is caused by several species of Candida, in addition to a limited number of systemic mycotic agents. While all microbial diagnostic assays face challenges before they are FDA approved and reach the market, there are a number of challenges to fungal diagnostic assay development that have been difficult hurdles to overcome. These hurdles include template preparation, fungal morphology, how many fungi should be identified in a single assay (scope), taxonomy and nomenclature, discriminating colonizers from invasive infection, combining identification with antifungal susceptibility, and navigating the administrative hurdles required to integrate an assay into a clinical laboratory. Some of these challenges are easier to overcome than others, but all seem to be particularly difficult for fungal diagnostic assays.

Keywords: antifungal; molds; mycoses; nomenclature; susceptibility testing; yeast.

FIG 1

Dimorphism in Candida albicans. C. albicans is an example of a dimorphic fungus. These fungi can grow as budding yeast or true septate hyphae. C. albicans also can produce pseudohyphae and, depending on culture conditions and duration, chlamydospores. Depending on the type of assay, morphology can affect the outcome or it can determine whether the culture can even be run on a specific assay or instrument. (A) C. albicans yeast cells grown in broth culture for 20 h. Bar = 10 μm. (B) C. albicans grown in broth culture showing predominantly hyphal growth. Bar = 10 μm. (C) C. albicans growing on agar medium as a typical yeast colony with a creamy texture and smooth surface. Bar = 1.0 cm. (D) C. albicans growing on agar medium showing a rough colony morphology that has hyphae growing under the colony. Bar = 1.0 cm. (Images courtesy of David Kadosh, reproduced with permission.)