title: 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.
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.
authors.affiliation: College of Life Sciences, Nanjing Normal University, Nanjing, 210032, China.|Institute for Comprehensive Utilization of Wild Plants, Nanjing, 210042, China.
authors.forename: Chengjie
authors.initials: C
authors.lastname: Shu
authors.affiliation: Key Laboratory of Developmental Genes and Human Disease in Ministry of Education, Medical School of Southeast University, Nanjing, 210009, China.
authors.forename: Lingmei
authors.initials: L
authors.lastname: Sun
authors.affiliation: College of Life Sciences, Nanjing Normal University, Nanjing, 210032, China. botanyzh@163.com.|Institute for Comprehensive Utilization of Wild Plants, Nanjing, 210042, China. botanyzh@163.com.
authors.forename: Weiming
authors.identifier: 0000-0002-1953-4016
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D018441:Biofilms / Q000187:drug effects; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000188:drug therapy* / Q000276:immunology; D048708:Cell Growth Processes / Q000187:drug effects; D007113:Immunity, Innate; D007422:Intestines / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D036122:Receptor, EphA4 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013943:Thymol / Q000627:therapeutic use*; D046930:Thymus Plant / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D029742:Caenorhabditis elegans Proteins; D013943:Thymol; D036122:Receptor, EphA4; D020928:Mitogen-Activated Protein Kinases; C463460:Pmk-1 protein, C elegans; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Caenorhabditis elegans; Candida albicans; Immunity; Thymol