Extremophilic organisms as an unexplored source of antifungal compounds

Extracts of the biomasses and fermentation broths of 217 extremophilic micr oorganisms isolated from a number of locales were screened for antifungal a ctivity using whole-cell and mechanism-based in vitro assays. Importantly, eleven broth extracts had activity against several Candida species and Aspe rgillus fumigatus in whole-cell in vitro assays. One broth specificallyinhi bited(1,3) beta -glucan synthase activity and four specifically inhibited k etol-isomerase activity, suggesting a mode of action of the antifungal comp ound(s) present in these extracts. The extract from one thermophile, a nove l species of Pseudomonas, was fractionated, an active compound purified and its structure determined. The compound was identified as pyochelin, a prev iously identified iron-binding compound with heretofore undescribed antifun gal activity. To our knowledge, this is the first report demonstrating that extremophiles synthesize compounds that have antifungal activity.