Chemosensitization prevents tolerance of Aspergillus fumigatus to antimycotic drugs |
| |
Authors: | Kim Jong Campbell Bruce Mahoney Noreen Chan Kathleen Molyneux Russell May Gregory |
| |
Institution: | a Plant Mycotoxin Research Unit, Western Regional Research Center, USDA-ARS, 800 Buchanan Street, Albany, CA 94710, USA b Division of Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA |
| |
Abstract: | Tolerance of human pathogenic fungi to antifungal drugs is an emerging medical problem. We show how strains of the causative agent of human aspergillosis, Aspergillus fumigatus, tolerant to cell wall-interfering antimycotic drugs become susceptible through chemosensitization by natural compounds. Tolerance of the A. fumigatus mitogen-activated protein kinase (MAPK) mutant, sakAΔ, to these drugs indicates the osmotic/oxidative stress MAPK pathway is involved in maintaining cell wall integrity. Using deletion mutants of the yeast, Saccharomyces cerevisiae, we first identified thymol and 2,3-dihydroxybenzaldehyde (2,3-D) as potent chemosensitizing agents that target the cell wall. We then used these chemosensitizing agents to act as synergists to commercial antifungal drugs against tolerant strains of A. fumigatus. Thymol was an especially potent chemosensitizing agent for amphotericin B, fluconazole or ketoconazole. The potential use of natural, safe chemosensitizing agents in antifungal chemotherapy of human mycoses as an alternative to combination therapy is discussed. |
| |
Keywords: | Aspergillus fumigatus Antifungal chemotherapy MAPK Chemosensitization Natural compounds Combination therapy |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|