国际口腔医学杂志

国际口腔医学杂志 ›› 2025, Vol. 52 ›› Issue (2): 210-216.doi: 10.7518/gjkq.2025029

• 论著 • 上一篇    下一篇

基于转录组学探讨金担子素A抗白色念珠菌的作用机制

易嘉欣1(),廖建春2,黄怡3,费伟4,郭骏3()   

  1. 1.电子科技大学医学院口腔医学系 成都 610072
    2.德阳市罗江区人民医院口腔科 德阳 618000
    3.四川省医学科学院·四川省人民医院口腔科 成都 610072
    4.四川省医学科学院 · 四川省人民医院（温江院区）口腔科 成都 611100
  • 收稿日期:2024-08-30 修回日期:2024-12-11 出版日期:2025-03-01 发布日期:2025-03-01
  • 通讯作者: 郭骏
  • 作者简介:易嘉欣，医师，硕士，Email：yijiaxin1999@163.com
  • 基金资助:
    四川省干部保健科研课题(2022-209)

Mechanism of action of aureobasidin A against Candida albicans based on transcriptomics analysis

Jiaxin Yi1(),Jianchun Liao2,Yi Huang3,Wei Fei4,Jun Guo3()   

  1. 1.Dept. of Stomatology, School of Medicine University of Electronic Science and Technology of China, Chengdu 610072, China
    2.Dept. of Stomatology, Luojiang District People’s Hospital in Deyang, Deyang 618000, China
    3.Dept. of Stomatology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu 610072, China
    4.Dept. of Stomatology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital (Wenjiang Campus), Chengdu 611100, China
  • Received:2024-08-30 Revised:2024-12-11 Online:2025-03-01 Published:2025-03-01
  • Contact: Jun Guo
  • Supported by:
    Sichuan Provincial Cadre Health Care Research Topic(2022-209)

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摘要：

目的 探究金担子素A（AbA）对白色念珠菌的抑菌活性及潜在作用机制，评估其未来作为新型抗真菌药物的应用潜力。 方法 首先测定了AbA的最低抑菌浓度（MIC），并探究其对菌丝形成及细胞壁完整性的影响。随后，利用转录组测序探讨了白色念珠菌在AbA作用下的响应机制。 结果 体外实验结果显示AbA的MIC值为0.062 5 μg/mL，并能显著抑制白色念珠菌的形态转换、破坏其细胞壁完整性。通过转录组测序共筛选出700个差异表达基因，其中上调基因465个，下调基因235个。京都基因（GO）富集分析结果显示：细胞外周、细胞质膜、真菌型细胞壁及氧化还原酶活性相关的通路最为富集。基因组百科全书（KEGG）富集分析结果表明代谢途径通路的富集程度最高。 结论 AbA对白色念珠菌具有较强的抑制作用，其潜在抗菌机制可能包括抑制菌丝形成、破坏细胞质膜、降低免疫逃逸能力以及抑制代谢活动。明确以上机制能够为制定更有效的抗真菌治疗策略提供重要理论依据。

关键词: 白色念珠菌, 金担子素A, 转录组测序, 基因组百科全书富集分析, 京都基因富集分析

Abstract:

Objective This study aimed to investigate the antibacterial activity and potential mechanism of aureobasi-dium A (AbA) against Candida albicans (C. albicans), as well as to evaluate its potential as a new antifungal drug in the future. Methods The minimum inhibitory concentration (MIC) of AbA was determined. The effect of MIC on mycelium formation and cell-wall integrity were investigated. Subsequently, transcriptome sequencing was used to investigate the response mechanism of C. albicans to AbA. Results In vitro results showed that the MIC of AbA was 0.062 5 μg/mL, and it significantly inhibited C. albicans morphogenesis and disrupted cell-wall integrity. Transcriptome sequencing identified 700 differentially expressed genes, including 465 upre-gulated and 235 downregulated genes. Gene ontology enrichment analysis revealed that pathways related to the extracellular region, plasma membrane, fungal cell wall, and redox enzyme activity were the most enriched. Enrichment analysis through the kyoto encyclopedia of genes and genomes indicated that the metabolic pathway was the most significantly enriched pathway. Conclusion AbA exhibited strong inhibitory activity against C. albicans. Its potential antimicrobial mechanisms may include inhibiting hyphal formation, disrupting the plasma membrane, reducing immune evasion, and suppressing metabolic activity. Understanding these mechanisms can provide valuable theoretical insights into the development of more effective antifungal-treatment strategies.

Key words: Candida albicans, aureobasidin A, transcriptome sequencing, kyoto encyclopedia of genes and genomes enrichment analysis, gene ontology enrichment analysis

中图分类号: 

  • R780.2

表 1

引物信息"

引物名称引物序列（5’—3’）
ALS3-FTACGCAACCACTACCATTACC
ALS3-RCACCTGGAGCAGTGATTGTAG
HWP1-FGCTCCTGCCACTGAACCTTCC
HWP1-RTTGGAGAAGAAGAAGCACCTGGAC
EFG1-FCGTTGCTGCTGCTACTACTACTG
EFG1-RTGAGGATACTGCTGTTGGTTGTAAG
EAP1-FGGGATGATTACAAGAAAG
EAP1-RGTGACGGTGATGATAGTG
TUP1-FCAACAGCAACAGCAGCAACAAC
TUP1-RACAACTGACGAGTGGTCTAAGGAG
GSP1-FTGAAGTCCATCCATTAGGAT
GSP1-RATCTCTATGCCAGTTTGGAA

图 1

倒置显微镜下观察AbA对白色念珠菌菌丝形成的影响A：对照组；B：1/2×MIC；C：1×MIC；D：2×MIC。"

图 2

AbA对白色念珠菌形态及菌丝形成的影响 SEM ×1 000AbA作用后细胞壁出现不同程度的皱缩破坏且均为酵母态细胞。A：对照组；B：8×MIC。"

图 3

实验组与AbA处理组白色念珠菌差异基因分布火山图红色代表上调基因、蓝色代表下调基因。"

图 4

AbA作用前后白色念珠菌差异表达基因的GO富集分析气泡图"

图 5

AbA作用前后白色念珠菌差异表达基因的KEGG富集分析"

图 6

AbA处理后ALS3、HWP1、EFG1、EAP1、TUP1基因表达量的统计学差异*：P<0.05；**：P<0.01， ***：P<0.001。"

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