The roles of CDR1, CDR2, and MDR1 in kaempferol-induced suppression with fluconazole-resistant Candida albicans

Abstract

Context: Fungal infections caused by fluconazole-resistant Candida albicans are an intractable clinical problem, calling for new efficient antifungal drugs. Kaempferol, an active flavonoid, has been considered a potential candidate against Candida species. Objective: This work investigates the resistance reversion of kaempferol in fluconazole-resistant C. albicans and the underlying mechanism. Materials and methods: The antifungal activities of fluconazole and/or kaempferol were assessed by a series of standard procedures including broth microdilution method, checkerboard assay and time-kill (T-K) test in nine clinical strains as well as a standard reference isolate of C. albicans. Subsequently, the morphological changes, the efflux of rhodamine 6G, and the expressions of CDR 1, CDR 2, and MDR 1 were analysed by scanning electron microscope (SEM), inverted fluorescence microscope and quantitative reverse transcription polymerase chain reaction (qRT-PCR) in C. albicans z2003.Results: For all the tested C. albicans strains, the minimum inhibitory concentrations (MICs) of fluconazole and kaempferol ranged 0.25-32 and 128-256 mg/mL with a range of fractional inhibitory concentration index of 0.257-0.531. In C. albicans z2003, the expression of both CDR 1 and CDR 2 were decreased after exposure to kaempferol alone with negligible rhodamine 6G accumulation, while the expression of CDR 1, CDR 2 and MDR 1 were all decreased when fluconazole and kaempferol were used concomitantly with notable fluorescence of rhodamine 6G observed. Discussion and conclusion: Kaempferol-induced reversion in fluconazole-resistant C. albicans might be likely due to the suppression of the expression of CDR1, CDR2 and MDR1.ARTICLE HISTORY

Radical Scavenging and Antimicrobial Properties of Polyphenol Rich Waste Wood Extracts

“…This could be explained by its richness of phenolic compounds which was observed in previous research [6]. For example, kaempferol is a potential candidate against different pathogenic microbes, and effective against fluconazole-resistant Candida albicans and Methicillin-resistant S. aureus (MRSA) [22]. In addition, galangin exhibited selective anti-cytochrome and antifungal activity [25], and showed antimicrobial activity against S. aureus [25,32], and methicillin-sensitive and methicillin-resistant S. aureus, Enterococcus spp., and P. aeruginosa [33].…”

“…Among flavonoids present in wild cherry wood, flavonols were distinguished by effective antimicrobial activity against resistant bacteria [22]. Methanolic extract (80%, v/v) from oak bark (Q. robur L.) showed moderate bactericidal, fungicidal, bacteriostatic and fungistatic activity on S. aureus, Enterobacter aerogenes (today known as Klebsiella aerogenes) and C. albicans [23].…”

Candida albicans Antifungal Resistance and Tolerance in Bloodstream Infections: The Triad Yeast-Host-Antifungal

“…Kaempferol, a flavonoid, exhibited a synergistic effect in C. albicans fluconazole resistant strains, by decreasing CDR1, CDR2, and MDR1 expression [163].…”

Kaempferol – A dietary anticancer molecule with multiple mechanisms of action: Recent trends and advancements

“…C. albicans z2003 128-256 lg/mL Shao, Zhang, Wang, Li, and Wang (2015) Foot associated with the composition of carbohydrate based food matrix. Rodriguez-Mateos, Oruna-Concha, Kwik-Uribe, Vidal, and Spencer (2012), demonstrated that the maltitol and sucrose were found to increase and decrease the absorption of flavonoids by altering the activity of catechol-O-methyltransferase (Rodriguez-Mateos et al, 2012).…”