https://scholars.lib.ntu.edu.tw/handle/123456789/573311
標題: | MSS2 maintains mitochondrial function and is required for chitosan resistance, invasive growth, biofilm formation and virulence in Candida albicans | 作者: | Ke C.-L Liao Y.-T Lin C.-H. CHING-HSUAN LIN |
關鍵字: | acetic acid; adenosine triphosphate; antimycin A1; carbon; chitosan; chloramphenicol; concanavalin A; deoxyribonuclease I; dodecyl sulfate sodium; fluorescein; glutamine; glycerol; mannitol; nourseothricin; oligonucleotide; paraformaldehyde; penicillin derivative; peptone; streptomycin; triton x 100; yeast extract; animal experiment; animal model; antifungal activity; antifungal resistance; antifungal susceptibility; Article; assay; biofilm; Candida albicans; cell culture; cell function; cell invasion assay; cell survival; fetal calf serum; fungal gene; fungal virulence; fungus growth; fungus hyphae; gene; gene deletion; gene expression; gene knockout; gene library; gene mutation; HeLa cell line; human; human cell; infant; male; mitochondrial biogenesis; mitochondrial function; mitochondrial respiration; mouse; MSS2 gene; NDT80 gene; nonhuman; oxygen consumption rate; pathogen load; plasmid; real time reverse transcription polymerase chain reaction; respiratory function; Saccharomyces cerevisiae; sensitivity assay; TEC1 gene | 公開日期: | 2021 | 卷: | 12 | 期: | 1 | 起(迄)頁: | 281-297 | 來源出版物: | Virulence | 摘要: | Candida albicans is the most prevalent fungal pathogen in humans, particularly in immunocompromised patients. In this study, by screening a C. albicans mutant library, we first identified that the MSS2 gene, an ortholog of Saccharomyces cerevisiae MSS2 required for mitochondrial respiration, mediates chitosan resistance. Upon treatment with 0.2% chitosan, the growth of mss2Δ strains was strikingly impaired, and MSS2 expression was significantly repressed by chitosan. Furthermore, mss2Δ strains exhibited slow growth on medium supplemented with glycerol as the sole carbon source. Similar to the chitosan-treated wild-type strain, the mss2Δ strain exhibited a significantly impaired ATP production ability. These data suggest that an antifungal mechanism of chitosan against C. albicans acts by inhibiting MSS2 gene expression, leading to repression of mitochondrial function. Normal respiratory function is suggested to be required for fungal virulence. Interestingly, the mss2Δ mutant strains exhibited significantly impaired invasive ability in vitro and ex vivo but retained normal hyphal development ability in liquid medium. Furthermore, the MSS2 deletion strains could not form robust biofilms and exhibited significantly reduced virulence. Collectively, these results demonstrated that the antifungal effect of chitosan against C. albicans is mediated via inhibition of mitochondrial biogenesis. These data may provide another strategy for antifungal drug development via inhibition of fungal mitochondria. ? 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85099304444&doi=10.1080%2f21505594.2020.1870082&partnerID=40&md5=bd3d3e0539893447f9e8a3c9d237bb02 https://scholars.lib.ntu.edu.tw/handle/123456789/573311 |
ISSN: | 21505594 | DOI: | 10.1080/21505594.2020.1870082 | SDG/關鍵字: | acetic acid; adenosine triphosphate; antimycin A1; carbon; chitosan; chloramphenicol; concanavalin A; deoxyribonuclease I; dodecyl sulfate sodium; fluorescein; glutamine; glycerol; mannitol; nourseothricin; oligonucleotide; paraformaldehyde; penicillin derivative; peptone; streptomycin; triton x 100; yeast extract; antifungal agent; chitosan; fungal protein; membrane protein; mitochondrial protein; MSS2 protein, S cerevisiae; Saccharomyces cerevisiae protein; animal experiment; animal model; antifungal activity; antifungal resistance; antifungal susceptibility; Article; assay; biofilm; Candida albicans; cell culture; cell function; cell invasion assay; cell survival; fetal calf serum; fungal gene; fungal virulence; fungus growth; fungus hyphae; gene; gene deletion; gene expression; gene knockout; gene library; gene mutation; HeLa cell line; human; human cell; infant; male; mitochondrial biogenesis; mitochondrial function; mitochondrial respiration; mouse; MSS2 gene; NDT80 gene; nonhuman; oxygen consumption rate; pathogen load; plasmid; real time reverse transcription polymerase chain reaction; respiratory function; Saccharomyces cerevisiae; sensitivity assay; TEC1 gene; animal; Candida albicans; candidiasis; drug effect; gene expression regulation; genetics; growth, development and aging; Institute for Cancer Research mouse; metabolism; microbiology; mitochondrion; pathogenicity; virulence; Animals; Antifungal Agents; Biofilms; Candida albicans; Candidiasis; Chitosan; Fungal Proteins; Gene Expression Regulation, Fungal; Humans; Hyphae; Male; Membrane Proteins; Mice; Mice, Inbred ICR; Mitochondria; Mitochondrial Proteins; Saccharomyces cerevisiae Proteins; Virulence |
顯示於: | 生化科技學系 |
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