Turbinmicin inhibits Candida biofilm growth by disrupting fungal vesicle-mediated trafficking
| Autor: | Fan Zhang, Kenneth J. Barns, Hiram Sanchez, Ryley Jones, Anjon Audhya, Robert Zarnowski, Jen Fossen, Tim S. Bugni, Miao Zhao, David R. Andes, Scott R. Rajski |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Chemistry Vesicle Concise Communication Biofilm Biofilm matrix General Medicine Drug resistance Extracellular vesicle biochemical phenomena metabolism and nutrition Isoquinolines Phenotype Microbiology Extracellular matrix 03 medical and health sciences Extracellular Vesicles 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis Biofilms Benzopyrans Biofilm growth Candida |
| Zdroj: | J Clin Invest |
| ISSN: | 1558-8238 |
| Popis: | The emergence of drug-resistant fungi has prompted an urgent threat alert from the US Centers for Disease Control (CDC). Biofilm assembly by these pathogens further impairs effective therapy. We recently identified an antifungal, turbinmicin, that inhibits the fungal vesicle-mediated trafficking pathway and demonstrates broad-spectrum activity against planktonically growing fungi. During biofilm growth, vesicles with unique features play a critical role in the delivery of biofilm extracellular matrix components. As these components are largely responsible for the drug resistance associated with biofilm growth, we explored the utility of turbinmicin in the biofilm setting. We found that turbinmicin disrupted extracellular vesicle (EV) delivery during biofilm growth and that this impaired the subsequent assembly of the biofilm matrix. We demonstrated that elimination of the extracellular matrix rendered the drug-resistant biofilm communities susceptible to fungal killing by turbinmicin. Furthermore, the addition of turbinmicin to otherwise ineffective antifungal therapy potentiated the activity of these drugs. The underlying role of vesicles explains this dramatic activity and was supported by phenotype reversal with the addition of exogenous biofilm EVs. This striking capacity to cripple biofilm assembly mechanisms reveals a new approach to eradicating biofilms and sheds light on turbinmicin as a promising anti-biofilm drug. |
| Databáze: | OpenAIRE |
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