title: Antifungal curcumin promotes chitin accumulation associated with decreased virulence of Sporothrix schenckii.
abstract: Curcumin, a yellow polyphenol compound, is known to possess antifungal activity for a range of pathogenic fungi. However, the fungicidal mechanism of curcumin (CUR) has not been identified. We have occasionally found that chitin redistributes to the cell wall outer layer of Sporothrix schenckii (S. schenckii) upon sublethal CUR treatment. Whether CUR can affect chitin synthesis via the protein kinase C (PKC) signaling pathway has not been investigated. This study describes a direct fungicidal activity of CUR against S. schenckii demonstrated by the results of a checkerboard microdilution assay and, for the first time, a synergistic effect of CUR with terbinafine (TRB). Furthermore, the results of real-time PCR showed that sublethal CUR upregulated the transcription of PKC, chitin synthase1 (CHS1), and chitin synthase3 (CHS3) in S. schenckii. The fluorescence staining results using wheat germ agglutinin-fluorescein isothiocyanate (WGA-FITC) and calcofluor white (CFW) consistently showed that chitin exposure and total chitin content were increased on the conidial cell wall of S. schenckii by sublethal CUR treatment. A histopathological analysis of mice infected with CUR-treated conidia showed dampened inflammation in the local lesion and a reduced fungal burden. The ELISA results showed proinflammatory cytokine secretion at an early stage from macrophages stimulated by the CUR-treated conidia. The present data led to the conclusion that CUR is a potential antifungal agent and that its fungicidal mechanism may involve chitin accumulation on the cell wall of S. schenckii, which is associated with decreased virulence in infected mice.
authors.affiliation: Department of Dermatology and Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Lilin
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Dermatology and Venereology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Tianzhang
authors.initials: T
authors.lastname: Song
authors.affiliation: Guangdong Provincial Center for Skin Diseases and STIs Control and Prevention, Guangzhou, Guangdong, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Hongling
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Dermatology and Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Tailong
authors.initials: T
authors.lastname: He
authors.affiliation: Department of Dermatology and Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Dermatology and Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: huxuchu@mail.sysu.edu.cn.
authors.forename: Xuchu
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Dermatology and Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: hhuaiqiu@medmail.com.cn.
authors.forename: Huaiqiu
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D002686:Chitin / Q000378:metabolism*; D002687:Chitin Synthase / Q000235:genetics / Q000378:metabolism; D003474:Curcumin / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009281:Naphthalenes / Q000627:therapeutic use; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D013175:Sporothrix / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D013174:Sporotrichosis / Q000188:drug therapy* / Q000276:immunology; D000077291:Terbinafine; D015854:Up-Regulation; D014774:Virulence
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D009281:Naphthalenes; D002686:Chitin; D002687:Chitin Synthase; C400821:chitin synthase 2; D011493:Protein Kinase C; D000077291:Terbinafine; D003474:Curcumin
keywords: Antifungal activity; Chitin; Curcumin; Sporothrix schenckii; Virulence