TY - JOUR A2 - Matsui, Reiko AU - Vriens, Kim AU - Kumar, Phalguni Tewari AU - Struyfs, Caroline AU - Cools, Tanne L. AU - Spincemaille, Pieter AU - Kokalj, Tadej AU - Sampaio-Marques, BelĂ©m AU - Ludovico, Paula AU - Lammertyn, Jeroen AU - Cammue, Bruno P. A. AU - Thevissen, Karin PY - 2017 DA - 2017/10/10 TI - Increasing the Fungicidal Action of Amphotericin B by Inhibiting the Nitric Oxide-Dependent Tolerance Pathway SP - 4064628 VL - 2017 AB - Amphotericin B (AmB) induces oxidative and nitrosative stresses, characterized by production of reactive oxygen and nitrogen species, in fungi. Yet, how these toxic species contribute to AmB-induced fungal cell death is unclear. We investigated the role of superoxide and nitric oxide radicals in AmB’s fungicidal activity in Saccharomyces cerevisiae, using a digital microfluidic platform, which enabled monitoring individual cells at a spatiotemporal resolution, and plating assays. The nitric oxide synthase inhibitor L-NAME was used to interfere with nitric oxide radical production. L-NAME increased and accelerated AmB-induced accumulation of superoxide radicals, membrane permeabilization, and loss of proliferative capacity in S. cerevisiae. In contrast, the nitric oxide donor S-nitrosoglutathione inhibited AmB’s action. Hence, superoxide radicals were important for AmB’s fungicidal action, whereas nitric oxide radicals mediated tolerance towards AmB. Finally, also the human pathogens Candida albicans and Candida glabrata were more susceptible to AmB in the presence of L-NAME, pointing to the potential of AmB-L-NAME combination therapy to treat fungal infections. SN - 1942-0900 UR - https://doi.org/10.1155/2017/4064628 DO - 10.1155/2017/4064628 JF - Oxidative Medicine and Cellular Longevity PB - Hindawi KW - ER -