Background: Multidrug-resistant (MDR) Candida auris is a global emerging pathogen responsible for nosocomial transmission and with current mortality rates ranging from 30-60%. It is associated with bloodstream, wound and ear infections. New antifungal therapies to address this serious threat are urgently needed. Methods: We screened a one-of-a-kind natural products library (Quave Natural Products Library, QNPL), consisting of >1,000 extracts from 400 plant and fungal species used in historical and current day traditional medical practices for human health (many for infectious disease), at 16 μg/mL by broth microtiter assay for antifungal activity against MDR isolates of Candida albicans. Next, we selected bioactive extract 429 - derived from a medicinal plant used for the treatment of wounds and various skin and soft tissue infection - from this initial screen for further MIC testing by broth microtiter dilution assay against MDR C. albicans and non-albicans Candida (NAC) species, including C. auris, C. glabrata, C. parapsilosis, and C. tropicalis. Results: The crude extract (429) and select partitions were active against all species tested, with MICs ≤2 μg/mL; the range of activity against C. auris isolates was from an MIC of 0.125-2 μg/mL. Cytotoxicity was assessed against human keratinocytes (HaCaTs) by LDH assay (IC50 > 32 μg/mL). The chemical makeup of 429 and its fractions were analyzed by LC-FTMS to yield putative compounds based on exact mass matches and fragmentation pattern analyses. Conclusions: To the best of our knowledge, this is the first report of activity by a medicinal plant extract against C. auris. This represents an important first starting point for the isolation and development of a novel drug to combat this critical emerging pathogen.
Full conference title:
- ASM Microbe 2nd (2017)