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In Vitro Interactions of Calcineurin Inhibitors with Conventional Antifungal Agents Against the Yeast Form of Penicillium marneffei

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Abstract

Penicillium marneffei can cause a life-threatening disseminated mycosis in immunocompromised hosts. However, therapeutic strategies for the treatment of this infectious disease are limited. Reports of other fungi suggest that calcineurin inhibitors interact with antifungal agents to improve the treatment outcomes. Here, we evaluated the in vitro interaction of the calcineurin inhibitors cyclosporine A and tacrolimus (FK506) combined with conventional antifungal agents against the pathogenic yeast form of P. marneffei. We demonstrate that the combination of cyclosporine A with amphotericin B, itraconazole, or fluconazole was synergistic for 85, 65, and 30 % of P. marneffei strains, respectively. In contrast, no synergism was observed in all the combinations containing tacrolimus. Furthermore, antagonism was not observed for any combination. In conclusion, the therapeutic potential of a combinatory approach using the calcineurin inhibitor cyclosporine A with conventional antifungal drugs may lead to improved treatment regimens for P. marneffei infections. We propose that mechanism of action studies with cyclosporine A and antifungal agents is needed.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81060128 and 81271804), Natural Science Foundation of Guangxi Province of China (No. 0991144 and 2012jjAA40175), a Guangxi Key Laboratory of AIDS Prevention and Treatment, and Specialized Research Fund for the Doctoral Program of Higher Education from the Ministry of Education of China (SRFDP, No. 20111106110032). The funders have no role in study design, data, collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China

    Dongdong Mo, Xin Li, Lili Wei & Cunwei Cao

  2. Chinese Academy of Medical Science and Peking Union Medical College, Institute of Medicinal Biotechnology, Beijing, 100730, China

    Chenghang Sun

  3. Center for AIDS Research and School of Public Health, Guangxi Medical University, Nanning, 530021, China

    Hao Liang

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  1. Dongdong Mo
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  2. Xin Li
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  3. Lili Wei
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  4. Chenghang Sun
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  6. Cunwei Cao
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Correspondence to Cunwei Cao.

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Dongdong Mo and Xin Li have equally contributed to this work.

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Mo, D., Li, X., Wei, L. et al. In Vitro Interactions of Calcineurin Inhibitors with Conventional Antifungal Agents Against the Yeast Form of Penicillium marneffei . Mycopathologia 178, 217–220 (2014). https://doi.org/10.1007/s11046-014-9787-8

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  • DOI: https://doi.org/10.1007/s11046-014-9787-8

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