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, Belém
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 -