Resveratrol Impaired the Morphological Transition of Candida albicans Under Various Hyphae-Inducing Conditions

Abstract

The ability of the human fungal pathogen Candida albicans to undergo the morphological transition from a single yeast form to pseudohyphal and hyphal forms in response to various conditions is known to be an important for its virulence. Many studies have shown the pharmacological effects of resveratrol, a phytoalexin polyphenolic compound. In this study, we investigated the antifungal activity of resveratrol against C. albicans. Both yeast-form and mycelial growth of C. albicans were inhibited by resveratrol. In addition, normal filamentation of C. albicans was affected and yeast-to-hypha transition under serum-, pH-, and nutrient-induced hyphal growth conditions was impaired by resveratrol.Key words Candida albicans; resveratrol (trans-3,4',-5-trihydroxystilebene); dimorphism 3 Candida albicans, a major fungal pathogen causing mucosal and systemic infections in immuno-compromised hosts [5,16], is dimorphic and grows as yeast as well as filamentous modes in host organisms and in vitro [19]. A key property of this fungus is its ability to switch from the yeast to the hyphal form in the host and this has been implicated in the process of pathogenesis since mutants defective in hyphal growth are known to be less virulent in systemic infections [15]. This transition is known to occur in response to a variety of environmental conditions, such as the presence of serum, body temperature (37°C), neutral pH, and growth with a poor carbon source [19].Resveratrol (trans-3,4',-5-trihydroxystilebene) is a phytoalexin polyphenolic compound produced by the innate host defense systems of plants [3,9]. Although many studies have shown various pharmacological effects of resveratrol, for instance, antiviral properties, protective effects against inflammation, enhancement of stress resistance, and lifespan extension [3,4,7], little is known about their effects on fungi. The antifungal activity of resveratrol was first demonstrated by Jung et al. [10,11]. However Weber et al. [21] recently mentioned that the potential candidacidal activity of resveratrol was not confirmed. The effective concentration of resveratrol against C. albicans observed by other groups varies considerably [6,13]. This suggests the difficulties still remain in the treatment with such biological agent. Therefore, there are great interests in the effects of resveratrol on C.albicans. The present study was designed to gain a better understanding the antifungal activity of resveratrol. We focused our attention on the examination of the effects of resveratrol on C. albicans growth, particularly the effects on morphological transition from single yeast cells to hyphal filaments under various hyphae-inducing conditions. (Fig. 2).For experiments involving hyphal growth, C. albicans yeast cell suspensions were spread on hyphae-inducing solid media without or with resveratrol and the colonies were photographed after 6-day incubation at 37°C. Resveratrol impairs the yeast-to-hyphae transition and induces colony morphological changes of C. albicans (Fig. 3). Normally, C....

In Vitro and In Vivo Activities of Pterostilbene against Candida albicans Biofilms

“…The effect of resveratrol (3,5,4-trihydroxystilbene), a close analogue of PTE, on C. albicans has been investigated previously (57)(58)(59). However, its antifungal effect was much weaker than PTE.…”

“…However, its antifungal effect was much weaker than PTE. More specifically, Okamoto et al revealed that the MIC 50 of resveratrol against C. albicans SC5314 was about 200 g/ml, and resveratrol (Ն40 g/ml) could inhibit the yeast-to-hypha morphological transition of C. albicans (57), while Collado et al (58) and Weber et al (59) reported that resveratrol had no antifungal activity against C. albicans. In this study, we found that PTE has a much stronger antifungal effect against C. albicans than resveratrol, with a MIC 80 of 32 g/ml and a minimal concentration in- hibiting morphological transition of 4 g/ml.…”

Styraxjaponoside A and B, Antifungal Lignan Glycosides Isolated from Styrax japonica S. et Z.

“…With respect to C. albicans, dimorphism plays a crucial role in the pathogenesis, with mycelial shapes being mainly found during a host tissue invasion ( Fig. 2A, B) Okamoto-Shibayama et al, 2010). The compounds exerted an inhibitory effect against the mycelial form of the C. albicans cells.…”

Modulation of Morphogenesis in Candida albicans by Various Small Molecules

“…While C. albicans does not possess a COX homolog, the fatty acid desaturase OLE2 and the multicopper oxidase FET3 were found to play a role in prostaglandin synthesis (40). Concurrently, several COX inhibitors, including diclofenac sodium, indomethacin, ibuprofen, resveratrol, and eicosatetraynoic acid (ETYA), were shown to block the Y-H transition induced in serum-containing, Lee's or Spider medium at 37°C (3,44,108,136). It is not clear whether or not COX inhibitors affected filamentation by blocking prostaglandin synthesis, given that a direct association between reduced prostaglandin levels and reduced hypha formation was not shown and that C. albicans does not encode a COX homolog.…”

“…Moreover, COX inhibitors appeared to reduce viability of C. albicans cells, which may account for their hypha-inhibiting activities (3,36,102). For instance, diclofenac sodium and resveratrol blocked hyphal development but also affected cellular growth (44,108).…”