The efflux pump inhibitor tetrandrine exhibits synergism with fluconazole or voriconazole against Candida parapsilosis

  • Ya-Jing Zhao
  • Wei-Da Liu
  • Yong-Nian Shen
  • Dong-Mei Li
  • Kun-Ju Zhu
  • Hong ZhangEmail author
Original Article


In the last two decades, with the wide use of azoles, antifungal resistance among Candida parapsilosis has considered a matter of concern worldwide. The aim of this study is to evaluate the antifungal potentials of tetrandrine (TET) alone and in combination with fluconazole (FLC)/voriconazole (VRC) against C. parapsilosis. Susceptibility tests were performed by microdilution method, checkerboard assay, time-kill test, spot assay. Subsequently, rhodamine 6G efflux test and the expressions of transporter related genes, namely CDR1 and MDR1 for C. parapsilosis were analyzed by qRT-PCR. The susceptibility test showed that TET presented strong synergism with FLC and VRC with fractional inhibitory concentration index (FICI) in a range of 0.094–0.562. The susceptibility results were also confirmed by spot assay and time-kill studies. With TET treatment, a vast quantity of rhodamine 6G could not be pumped out from the cells as considerably intracellular red fluorescence was accumulated. Meanwhile, the expressions of efflux-associated genes presented varying degrees of inhibition. These results indicated that TET was a decent antifungal synergist to promote the antifungal efficacy of FLC/VRC, and the underlying antifungal mechanism might be associated with the inhibition of efflux pump and the elevation of intracellular drug content.


Tetrandrine (TET) Fluconazole (FLC) Voriconazole (VRC) Candida parapsilosis Synergism 


Author contributions

All the authors conceived the study, participated in its design and coordination and collected and managed the data. YZ drafted the manuscript, and all authors contributed substantially to its revision. All the authors read and approved the final manuscript.


This work was supported by the National Nature Science Foundation of China (Grant No. 81471995).

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Ya-Jing Zhao
    • 1
    • 2
  • Wei-Da Liu
    • 3
  • Yong-Nian Shen
    • 3
  • Dong-Mei Li
    • 4
  • Kun-Ju Zhu
    • 1
    • 2
  • Hong Zhang
    • 1
    • 2
    Email author
  1. 1.The First Affiliated Hospital of Jinan UniversityGuangzhouChina
  2. 2.Institute of MycologyJinan UniversityGuangzhouChina
  3. 3.Department of Mycology, Institute of DermatologyChinese Academy of Medical Science and Peking Union Medical CollegeNanjingChina
  4. 4.Department of Microbiology and ImmunologyGeorgetown University Medical CenterWashingtonUSA

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