Curcumin potentiates the fungicidal effect of dodecanol by inhibiting drug efflux in wild‐type budding yeast

Abstract

Significance and Impact of the Study: Drug resistance is common in immunocompromised patients with fungal infections. Curcumin, isolated from Curcuma longa, inhibits drug efflux in nonpathogenic budding yeast Saccharomyces cerevisiae cells overexpressing ABC transporters S. cerevisiae Pdr5p and pathogenic Candida albicans Cdr1p and Cdr2p. We examined the effects of curcumin on multidrug resistance in a wild-type strain of the budding yeast with an intrinsic expression system of multidrug efflux-related genes. Curcumin directly inhibited drug efflux and also suppressed the PDR5 expression, thereby enhancing the antifungal effects. Thus, curcumin potentially promotes the efficacy of antifungals via its effects on ABC transporters in wild-type fungal strains. AbstractDrug resistance commonly occurs when treating immunocompromised patients who have fungal infections. Curcumin, is a compound isolated from Curcuma longa, has been reported to inhibit drug efflux in several human cell lines and nonpathogenic budding yeast Saccharomyces cerevisiae cells that overexpresses the ATP-binding cassette (ABC) transporters S. cerevisiae Pdr5p and pathogenic Candida albicans Cdr1p and Cdr2p. The aim of this study was to examine the effects of curcumin on multidrug resistance in a wild-type strain of the budding yeast with an intrinsic expression system of multidrug efflux-related genes. The antifungal activity of dodecanol alone was temporary against S. cerevisiae; however, restoration of cell viability was completely inhibited when the cells were co-treated with dodecanol and curcumin. Furthermore, restriction of rhodamine 6G (R6G) efflux from the cells and intracellular accumulation of R6G were observed with curcumin treatment. Reverse transcription-polymerase chain reaction analysis revealed that curcumin reduced the dodecanol-induced overexpression of the ABC transporter-related genes PDR1, PDR3 and PDR5 to their control levels in untreated cells. Curcumin can directly restrict the glucose-induced drug efflux and inhibits the expression of the ABC transporter gene PDR5, and can thereby inhibit the efflux of dodecanol from S. cerevisiae cells. Curcumin is effective in potentiating the efficacy of antifungal drugs via its effects on ABC transporters.

Plant Phytochemicals in Food Preservation: Antifungal Bioactivity: A Review

“…Curcumin is also active against Sporothrix schenckii, the cause of sporotrichosis, redistributing chitin in its cell wall (38). The activity of this compound can be modified in combination with other molecules, such as dodecanol or ascorbic acid (42,95). This antifungal activity could reside in the induction of alterations of membrane-associated ATPases, ergosterol biosynthesis inhibition, and reduction in the levels of proteinase secretion, an important virulence factor (60,95).…”

“…The activity of this compound can be modified in combination with other molecules, such as dodecanol or ascorbic acid (42,95). This antifungal activity could reside in the induction of alterations of membrane-associated ATPases, ergosterol biosynthesis inhibition, and reduction in the levels of proteinase secretion, an important virulence factor (60,95). However, curcumin is insoluble in water, so it must be microencapsulated to be used as a preservative in food, thereby increasing the solubility and antifungal effect of curcumin (14,31).…”

Structure–activity relationships of antifungal phenylpropanoid derivatives and their synergy with n ‐dodecanol and fluconazole

“…Assays were performed as described (Yamawaki et al 2018(Yamawaki et al , 2019. Serial, twofold dilutions of the compounds were prepared in DMF.…”

“…Assays were performed as previously described (Yamawaki et al 2019). Yeast cells cultured overnight in YPD broth were centrifuged at 5000 9 g for 5 min at 27°C.…”

Protective Effect of Kickxia ramosissima (Wall.) Janchn Extracts Against Pathogenic Bacterial Strains and Free Radicals

“…Different studies depicted that a large range of plant products including polyphenols, terpenes and various plant extracts show an antioxidant as well as microbicidal action [3]. Ethnobotanical data have proved useful in the search for new antimicrobial agents, and many of these compounds have been isolated directly from medicinal plants [4].…”