There is an urgent and unmet need for new antifungal therapies. Global fungal infection rates continue to rise and fungal infections pose increasing burdens on global healthcare systems. Exacerbating the situation, the available antifungal therapeutic arsenal is limited and development of new antifungals has been slow. Current antifungals are known for unwanted side effects including nephrotoxicity and hepatotoxicity. Thus, the need for new antifungals and new antifungal targets is urgent and growing. A collection of 60 commercially-available essential oils has been screened for antifungal activity against Aspergillus niger, Candida albicans, and Cryptococcus neoformans, as well as for cytotoxic activity against MCF-7 and MDA-MB-231 human breast tumor cell lines; the chemical compositions of the essential oils have been determined by gas chromatography-mass spectrometry (GC-MS). Ten essential oils showed remarkable antifungal and cytotoxic activities: Indian, Australian, and Hawaiian sandalwoods; melissa; lemongrass; cilantro; cassia; cinnamon; patchouli; and vetiver.
New antibiotics and new antibiotic targets are needed to counter the development of bacterial drug resistance that threatens to return the human population to the pre-antibiotic era. Bacterial peptidyl-tRNA hydrolase (Pth1) is a promising new antibiotic target in the early stages of development. While inhibitory activity has been observed in a variety of natural products, bioactive fractionation has been a bottleneck for inhibitor isolation. To expedite the isolation of inhibitory compounds from complex mixtures, we constructed a Pth1 affinity column and used it to isolate inhibitory compounds from crude natural products. Recombinantly produced S. typhimurium Pth1 was covalently attached to a column matrix and the inhibitory activity isolated from ethanol extracts of Salvinia minima. The procedure reported here demonstrates that isolation of Pth1 inhibitory compounds from complex natural product extracts can be greatly expedited over traditional bioactive fractionation, decreasing time and expense. The approach is generally applicable to Pth1s from other bacterial species and opens an avenue to advance and accelerate inhibitor development against this promising antimicrobial target.
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