Molecular mechanisms underlying the tetrandrine-mediated reversal of the fluconazole resistance of<i>Candida albicans</i>

Zhang, Xiaoli; Guo, Hui; Gao, Lai-qiang; Song, Yanjun; Li, Shuixiu; Zhang, Hong

doi:10.3109/13880209.2013.764537

Cited by 12 publications

(6 citation statements)

References 19 publications

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“…Mitochondrial complex V activity was measured by an assay kit according to the manufacturer’s protocol. For determinations of intracellular ATP concentrations, an aliquot of 1 × 10 6 cells from each strain was mixed with the same volume of BacTiter-GloTM reagent (Promega Corporation, Madison, WI, USA) and incubated for 5 min at room temperature as described previously ( Zhang et al, 2013 ). ROS measurement was performed by using a oxidation-sensitive fluorescent dye DCFDA ( Guo et al, 2014 ).…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial Complex V α Subunit Is Critical for Candida albicans Pathogenicity through Modulating Multiple Virulence Properties

Song

Zhang

et al. 2017

Front. Microbiol.

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The α subunit (ATP1) is a vital component of mitochondrial complex V which counts for the majority of cellular ATP production in a living organism. Nevertheless, how the α subunit influences other cellular processes such as pathogenicity in Candida albicans remains poorly understood. To address this question, ATP1 mutant (atp1Δ/Δ) and the gene-reconstituted strain (atp1Δ/ATP1) have been constructed in this study and their pathogenicity-related traits are compared to those of wild type (WT). In a murine model of disseminated candidiasis, atp1Δ/Δ infected mice have a significantly higher survival rate and experience a lower fungal burden in tissues. In in vitro studies atp1Δ/Δ lose a capability to damage or destroy macrophages and endothelial cells. Furthermore, atp1Δ/Δ is not able to grow under either glucose-denial conditions or high H2O2 conditions, both of which are associated with the potency of the macrophages to kill C. albicans. Defects in filamentation and biofilm formation may impair the ability of atp1Δ/Δ to penetrate host cells and establish robust colonies in the host tissues. In concert with these pathogenic features, intracellular ATP levels of atp1Δ/Δ can drop to 1/3 of WT level. These results indicate that the α subunit of Complex V play important roles in C. albicans pathogenicity.

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Section: Methodsmentioning

confidence: 99%

Mitochondrial Complex V α Subunit Is Critical for Candida albicans Pathogenicity through Modulating Multiple Virulence Properties

Song

Zhang

et al. 2017

Front. Microbiol.

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“…Several chemicals from traditional herbs, such as tetrandrine (Zhang et al 2013) and allicin (Khodavandi et al 2011), have been recognised as alternatives to enhance the antifungal activity of FLC. Flavonoids are a group of chemicals, and have also been reported to have broad-spectrum antibacterial and antifungal activities (Friedman 2007;Orhan et al 2010;Peralta et al 2012).…”

Section: Introductionmentioning

confidence: 99%

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

Shao

Zhang

Wang

et al. 2015

Pharmaceutical Biology

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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

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“…A recent study indicated that TET could inhibit the expression of MDR1, FLU1, CDR1, CDR2 and reduce drug efflux and increase the accumulation of intracellular azoles, thereby enhancing the sensitivity of C. albicans to FLC (Zhang et al . , 2013a). Zhang et al .…”

Section: The Antifungal Activity Of Traditional Chinese Medicinementioning

confidence: 99%

“…At present, research on the synergistic antifungal mechanism between TET and azoles has also been reported. A recent study indicated that TET could inhibit the expression of MDR1, FLU1, CDR1, CDR2 and reduce drug efflux and increase the accumulation of intracellular azoles, thereby enhancing the sensitivity of C. albicans to FLC (Zhang et al 2009(Zhang et al , 2013a. Zhang et al (2013b) also found that the synergistic mechanism of FLC and TET against C. albicans was related to inhibition of the drug efflux system by proteomic analysis.…”

Section: Tetrandrinementioning

confidence: 99%

Antifungal activity of immunosuppressants used alone or in combination with fluconazole

et al. 2018

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Summary Fungal infections remain a challenge to clinicians due to the limited available antifungals. With the increasing use of antifungals in clinical practice, drug resistance has been emerging continuously, especially to fluconazole (FLC). Thus, a search for new antifungals and approaches to overcome antifungal resistance is needed. However, the development of new antifungals is usually costly and time consuming; discovering the antifungal activity of non‐antifungal agents is one way to address these problems. Interestingly, some researchers have demonstrated that several classes of immunosuppressants (calcineurin inhibitors, glucocorticoids, etc) also displayed potent antifungal activity when used alone or in combination with antifungals, especially with FLC. Some of them could increase FLC's susceptibility against resistant Candida albicans significantly reversing fungal resistance to FLC. This article reviews the antifungal activities of immunosuppressants used alone or in combination with antifungals and their potential antifungal mechanisms that have been discovered so far. Although immunosuppressive agents have been identified as risk factors for fungal infection, we believe these findings are very important for overcoming drug resistance and developing new antifungals.

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Molecular mechanisms underlying the tetrandrine-mediated reversal of the fluconazole resistance ofCandida albicans

Cited by 12 publications

References 19 publications

Mitochondrial Complex V α Subunit Is Critical for Candida albicans Pathogenicity through Modulating Multiple Virulence Properties

Mitochondrial Complex V α Subunit Is Critical for Candida albicans Pathogenicity through Modulating Multiple Virulence Properties

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

Antifungal activity of immunosuppressants used alone or in combination with fluconazole

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