Oxidative stress response to menadione and cumene hydroperoxide in the opportunistic fungal pathogen Candida glabrata

The Facultative Intracellular Pathogen Candida glabrata Subverts Macrophage Cytokine Production and Phagolysosome Maturation

“…The oxidative stress response of C. glabrata is controlled by the transcription factors Yap1, Skn7, Msn2, and Msn4 (30,60,61), which mediate resistance of C. glabrata to H 2 O 2 and other oxidants. Additionally, C. glabrata possesses a catalase (Cta1p) that is required to survive oxidative stress (although this is dispensable in a mouse model of systemic infection) (60,62). In agreement with a previous study, which showed that C. glabrata can suppress the release of oxidants during its interaction with a murine macrophage cell line (21), in this study we demonstrate repression of ROS production by primary human macrophages.…”

Heterocycle Thiazole Compounds Exhibit Antifungal Activity through Increase in the Production of Reactive Oxygen Species in the Cryptococcus neoformans-Cryptococcus gattii Species Complex

“…However, the combination of thiazoles with diamide, a thiol oxidizing agent, and hydrogen peroxide had no effect, suggesting that oxidative stress is not caused by an accumulation of oxides and peroxides. Menadione is able to generate superoxide (31,32), and the synergism may indicate that the thiazoles lead to superoxide accumulation inside the cell, culminating in yeast death. Additionally, we sought to determine if there was synergy with RNS by testing peroxynitrite, a highly reactive nitrogen species formed from the reaction of nitric oxide (NO) and superoxide, and FeTPPS, a ferric porphyrin complex that causes the decomposition of peroxynitrite by catalytic isomerization to produce nitrate both in vitro and in vivo.…”

Proteomic analysis of cell wall in four pathogenic species of Candida exposed to oxidative stress

“…As shown in Figures 1A and B, the cells were exposed to two different concentrations of H 2 O 2 or menadione (O 2 •‾ ), which were chosen based on previous studies where we determined how the four species respond to the OS during the stationary and logarithmic phases [17,27]. Accordingly, concentrations of H 2 O 2 were 150 and 300 mM for C. albicans; 300 and 500 mM for C. glabrata and C. parapsilosis; and 500 and 1500 mM for C. krusei, and in the case In each case, at the lower concentration, oxidant-exposed cells showed the same growth as control cells while at the higher concentration a significant decrease in growth was observed [12,13,17,27]. As shown in Figures 1A and 1B, CWP from both treated and untreated cells of the four species resolved into well-defined bands.…”

“…This is essential, because the CWP that allow the organism to adhere to the host, are potent immunomodulators as antifungal targets, which have not yet been found in humans. In addition, it will allow to elucidate whether CWP may represent an enzymatic mechanism of ROS detoxification as in previous communications it has been shown that each Candida species responds differentially to these agents [12,13,17,30,33,34]. To get an insight into the role of CWP in the response of Candida CWP to ROS, we used a proteomic approach to identify the CWP of four species of Candida that regulate their expression during OSR.…”

“…Thus, C. albicans is the most susceptible species to H 2 O 2 as compared with C. glabrata, C. krusei and C. parapsilosis[12,13,17,27,35] but, paradoxically, being the most frequent agent of invasive candidiasis, of C. krusei and C. parapsilosis to H 2 O 2 may be due to the presence of an oxidase which is part of an alternative oxidative pathway[32,38,39]. This suggests the existence of alternative mechanisms to detoxify ROS that may include CWP.…”