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TitleIncreasing the fungicidal action of Amphotericin B by inhibiting the Nitric Oxide-Dependent tolerance pathway
Kumar, Phalguni Tewari
Struyfs, Caroline
Cools, Tanne L.
Spincemaille, Pieter
Kokalj, Tadej
Marques, Belém Sampaio
Ludovico, Paula
Lammertyn, Jeroen
Cammue, Bruno P. A.
Thevissen, Karin
Issue date10-Oct-2017
PublisherHindawi Publishing Corporation
JournalOxidative Medicine and Cellular Longevity
Abstract(s)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.
Publisher version
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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