Glucose Directly Promotes Antifungal Resistance in the Fungal Pathogen, Candida spp. [Molecular Bases of Disease]

August 8th, 2014 by Mandal, S. M., Mahata, D., Migliolo, L., Parekh, A., Addy, P. S., Mandal, M., Basak, A.

Effects of glucose on the susceptibility of antifungal agents are investigated against Candida spp. Increasing the concentration of glucose decreased the activity of antifungal agents, voriconazole was mostly affected drugs followed by amphotericin B. No significant change has been observed for anidulafungin. Biophysical interaction between antifungal agents with glucose molecules were investigated using ITC, FTIR and 1HNMR. Glucose have higher affinity to bind with voriconazole by hydrogen bonding and decrease the susceptibility. In addition to confirm the results observed in vitro, theoretical docking studies demonstrated that voriconazole presented three important hydrogen bonds and amphotericin B presented two hydrogen bonds that stabilized the complex compound-glucose. In vivo results also suggest that the physiologically relevant higher glucose level in blood stream of diabetes mellitus (DM) mice might interact with the available selective agents during antifungal therapy, decreased the activity by complex formation. Thus, selection of drugs for DM patient is important to control the infectious diseases.