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Thymol has antifungal activity against Candida albicans during infection and maintains the innate immune response required for function of the p38 MAPK signaling pathway in Caenorhabditis elegans

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Abstract

The Caenorhabditis elegans model can be used to study Candida albicans virulence and host immunity, as well as to identify plant-derived natural products to use against C. albicans. Thymol is a hydrophobic phenol compound from the aromatic plant thyme. In this study, the in vitro data demonstrated concentration-dependent thymol inhibition of both C. albicans growth and biofilm formation during different developmental phases. With the aid of the C. elegans system, we performed in vivo assays, and our results further showed the ability of thymol to increase C. elegans life span during infection, inhibit C. albicans colony formation in the C. elegans intestine, and increase the expression levels of host antimicrobial genes. Moreover, among the genes that encode the p38 MAPK signaling pathway, mutation of the pmk-1 or sek-1 gene decreased the beneficial effects of thymol’s antifungal activity against C. albicans and thymol’s maintenance of the innate immune response in nematodes. Western blot data showed the level of phosphorylation of pmk-1 was dramatically decreased against C. albicans. In nematodes, treatment with thymol recovered the dysregulation of pmk-1 and sek-1 gene expressions, the phosphorylation level of PMK-1 caused by C. albicans infection. Therefore, thymol may act, at least in part, through the function of the p38 MAPK signaling pathway to protect against C. albicans infection and maintain the host innate immune response to C. albicans. Our results indicate that the p38 MAPK signaling pathway plays a crucial role in regulating the beneficial effects observed after nematodes infected with C. albicans were treated with thymol.

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Acknowledgments

This study was supported by the National Program during the 12th Five-year Plan Period, high ecological utilization for regional specialty resources (2012BAD36B01), Grants from the National Natural Science Foundation of China (No. 81302814), and Natural Science Foundation of Jiangsu Province (No. BK20130640).

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    Authors and Affiliations

    1. College of Life Sciences, Nanjing Normal University, Nanjing, 210032, China

      Chengjie Shu & Weiming Zhang

    2. Institute for Comprehensive Utilization of Wild Plants, Nanjing, 210042, China

      Chengjie Shu & Weiming Zhang

    3. Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Medical School of Southeast University, Nanjing, 210009, China

      Lingmei Sun

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    1. Chengjie Shu
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    Correspondence to Weiming Zhang.

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    Human and animal rights statement

    All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.

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    Informed consent was obtained from all individual participants included in the study.

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    Chengjie Shu and Lingmei Sun have contributed equally to this work.

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    Shu, C., Sun, L. & Zhang, W. Thymol has antifungal activity against Candida albicans during infection and maintains the innate immune response required for function of the p38 MAPK signaling pathway in Caenorhabditis elegans . Immunol Res 64, 1013–1024 (2016). https://doi.org/10.1007/s12026-016-8785-y

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