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Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
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Synergistic Effect of Fluconazole and Calcium Channel Blockers against Resistant Candida albicans

Shuyuan Liu1,2, Longtao Yue3, Wenrui Gu1

  • 1School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, Shandong Province, People's Republic of China.

Plos One
|March 18, 2016
PubMed

Insights

This study found that combining calcium channel blockers (CCBs) like amlodipine with fluconazole shows synergistic antifungal effects against resistant Candida albicans strains. This combination therapy offers a promising strategy to combat emerging drug resistance in fungal infections.

Area of Science:

  • Mycology
  • Pharmacology
  • Infectious Diseases

Background:

  • Candidiasis is a growing threat, especially in immunocompromised patients.
  • Limited antifungal drugs and increasing fungal resistance necessitate novel therapeutic approaches.
  • Combination drug therapy is an effective strategy to overcome antifungal resistance.

Purpose of the Study:

  • To evaluate the combined antifungal effects of four calcium channel blockers (CCBs) with fluconazole against Candida albicans.
  • To investigate the potential mechanisms underlying the synergistic interactions.
  • To assess the efficacy against both sensitive and resistant strains.

Main Methods:

  • Checkerboard and time-killing assays were used to determine combined antifungal activity.
  • Quantitative PCR was employed to analyze gene expression levels.
  • Rhodamine 6G assay was utilized to measure efflux pump activity in resistant C. albicans.

Main Results:

  • Synergistic antifungal activity (FICI < 0.5) was observed when fluconazole was combined with amlodipine, nifedipine, benidipine, and flunarizine against resistant C. albicans strains.
  • No significant interaction was found against sensitive strains (FICI = 0.56–2).
  • Combination therapy, particularly fluconazole plus amlodipine, downregulated genes associated with calcineurin and vacuolar calcium channels (CNA1, CNB1, YVC1).

Conclusions:

  • Calcium channel blockers (CCBs) in combination with fluconazole demonstrate significant synergistic effects against resistant Candida albicans.
  • This combination therapy represents a potential strategy to overcome fluconazole resistance in C. albicans.
  • Downregulation of specific genes involved in calcineurin and calcium transport pathways may contribute to the observed synergistic effect.

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