Glutathione protects Candida albicans against horseradish volatile oil

Abstract

Horseradish essential oil (HREO; a natural mixture of different isothiocyanates) had strong fungicide effect against Candida albicans both in volatile and liquid phase. In liquid phase this antifungal effect was more significant than those of its main components allyl, and 2-phenylethyl isothiocyanate. HREO, at sublethal concentration, induced oxidative stress which was characterized with elevated superoxide content and up-regulated specific glutathione reductase, glutathione peroxidase, catalase and superoxide dismutase activities. Induction of specific glutathione S-transferase activities as marker of glutathione (GSH) dependent detoxification was also observed. At higher concentration, HREO depleted the GSH pool, increased heavily the superoxide production and killed the cells rapidly. HREO and the GSH pool depleting agent, 1-chlore-2,4-dinitrobenzene showed strong synergism when they were applied together to kill C. albicans cells. Based on all these, we assume that GSH metabolism protects fungi against isothiocyanates.

Endophytic fungi from the roots of horseradish (Armoracia rusticana) and their interactions with the defensive metabolites of the glucosinolate - myrosinase - isothiocyanate system

“…AITC spontaneously conjugates with the thiol pool of the fungi (mainly GSH [ 50 ]) and is in part released into the medium. ITC toxicity increases when the GSH pool of the fungi becomes depleted [ 16 ], resulting in increased attack on the protein -SH groups. The rapid recovery of GSH from the conjugate could result in such a low detected amounts of GSH-AITC (Fig.…”

“…As the phenomenon is extremely overlaid by interspecies variability, further studies will be necessary to provide further evidence on this logically expectable adaptation to ITCs. The background mechanisms behind the adaptation likely include genes that enable enhanced recycling or excessive production of thiols [ 27 ], such as GSH [ 16 , 50 ]. This can lead to resistance to fungicides that target the thiol pool of phytopathogenic fungi [ 57 , 58 ].…”

“…The isothiocyanates were shown to have potent antifungal activity in many papers (e.g. [ 14 – 16 ]). It is an interesting question how endophytes tolerate the isothiocyanates of the plants.…”

Ebselen exerts antifungal activity by regulating glutathione (GSH) and reactive oxygen species (ROS) production in fungal cells

“…The presence of low amount of GSH in these deletion strains was further depleted by ebselen treatment and in turn places cells in oxidative stress. Importance and essentiality of GSH has also been demonstrated in other fungi species including Candida [60,65], suggesting that glutathione might form an attractive novel target for the development of new antifungal drugs [66–68]. Future studies are required to delineate the interaction between ebselen and yeast GSH, and also the affinity of ebselen towards mammalian GSH.…”

Glutathione and Its Implications During Candida Infections in Humans.

“…Horseradish essential oil (HREO) is a mixture of different isothiocyanates having a antifungal activity against Candida albicans is also acting by production of ROS. In C. albicans it leads to depletion of GSH and increase in hydrogen peroxide, damaging the cells (Bertoti et al, 2016;Yadav et al, 2011). Furthermore, Ebselen; a mimic of GSH peroxidase has been shown recently to have antifungal activity against Candida by depletion of GSH and increase in ROS in cells (Thangamani et al, 2017).…”