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Kim Vriens [1] and Phalguni Tewari Kumar [2] and Caroline Struyfs [1; 3] and Tanne L. Cools [1] and Pieter Spincemaille [4] and Tadej Kokalj [2] and Belém Sampaio-Marques [5; 6] and Paula Ludovico [5; 6] and Jeroen Lammertyn [2] and Bruno P. A. Cammue [1; 3] and Karin Thevissen [1]

Academic Editor: Reiko Matsui

1, Centre of Microbial and Plant Genetics, KU Leuven, 3001 Heverlee, Belgium, kuleuven.be

2, BIOSYST-MEBIOS, KU Leuven, 3001 Heverlee, Belgium, kuleuven.be

3, VIB Department of Plant Systems Biology, 9052 Ghent, Belgium, vib.be

4, Department of Laboratory Medicine, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium, uzleuven.be

5, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal, uminho.pt

6, ICVS/3B’s-PT Government Associate Laboratory, Braga/Guimarães, Portugal, uminho.pt

Received May 18, 2017; Accepted Aug 2, 2017

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1. Introduction

Pathogenic fungi, including Candida albicans and Candida glabrata, encounter diverse environmental stresses when colonizing human tissues. During the infection process, they are exposed to potent reactive oxygen and nitrogen species (ROS and RNS, resp.), including nitric oxide radical (NO•), peroxynitrite (ONOO−), superoxide anion radical (O2−•), and hydroxyl radical (•OH), generated by the respiratory burst of phagocytic cells [1–3]. ROS and RNS cause damage to DNA, proteins, and lipids and are toxic to most fungi [4, 5]. In contrast to most nonpathogenic fungi, fungal pathogens such as several Candida species have developed responses to neutralize these toxic radicals and repair the potential molecular damage [6]. In this respect, various proteins that protect the fungus from oxidative and nitrosative stresses have been identified and include signalling proteins, transcription factors, and a variety of other enzymes such as catalases, superoxide dismutases, peroxidases, and nitric oxide dioxygenase [1, 7]. Hence, antifungals (or combinations thereof) inducing an excess ROS and/or RNS in a pathogenic fungus that cannot be neutralized by its endogenous protection mechanisms are of great interest [8].

Many antifungal agents are reported to induce oxidative (excess ROS) stress in pathogenic fungi. These agents include small molecules, such as miconazole [9, 10],...

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