基于转录组学探讨金担子素A抗白色念珠菌的作用机制  

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

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作  者:易嘉欣 廖建春 黄怡 费伟[4] 郭骏[3] Yi Jiaxin;Liao Jianchun;Huang Yi;Fei Wei;Guo Jun(Dept.of Stomatology,School of Medicine University of Electronic Science and Technology of China,Chengdu 610072,China;Dept.of Stomatology,Luojiang District People’s Hospital in Deyang,Deyang 618000,China;Dept.of Stomatology,Sichuan Academy of Medical Sciences&Sichuan Provincial People’s Hospital,Chengdu 610072,China;Dept.of Stomatology,Sichuan Academy of Medical Sciences&Sichuan Provincial People’s Hospital(Wenjiang Campus),Chengdu 611100,China)

机构地区:[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

出  处:《国际口腔医学杂志》2025年第2期210-216,共7页International Journal of Stomatology

基  金:四川省干部保健科研课题(2022-209)。

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0.0625μg/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。Objective This study aimed to investigate the antibacterial activity and potential mechanism of aureobasidium 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 0.0625μg/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.

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 

分 类 号:R780.2[医药卫生—口腔医学]

 

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