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中国真菌学杂志 2016, Vol. 11  Issue (3): 135-139.

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秀丽隐杆线虫-白念珠菌感染模型用于抗真菌药效评价的研究

毕爽, 胡淦海, 胡丹丹, 姜远英, 王彦   

  1. 中国人民解放军第二军医大学药学院新药研究中心, 上海 200433
  • 收稿日期:2015-10-14 出版日期:2016-06-28 发布日期:2016-06-28
  • 通讯作者: 王彦,E-mail:wangyansmmu@126.com E-mail:wangyansmmu@126.com
  • 作者简介:毕爽,女(汉族),硕士研究生在读.E-mail:shuangxun640@126.com;胡淦海,男(汉族),硕士.E-mail:349803307@qq.com
  • 基金资助:

    国家自然科学基金(81273558,81072678);上海市浦江人才计划(14PJD001)

Evaluation of antifungal drugs using a Caenorhabditis elegans-Candida albicans infection model

BI Shuang, HU Dan-dan, JIANG Yuan-ying, WANG Yan   

  1. New Drug Research and Development Center, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
  • Received:2015-10-14 Online:2016-06-28 Published:2016-06-28

摘要:

目的 观察秀丽隐杆线虫-白念珠菌感染模型用于抗真菌药效评价的可靠性和稳定性,评价该模型在抗真菌药物研发中的应用价值。方法 使线虫吞食白念珠菌造成致死性感染,建立线虫-白念珠菌感染模型,选用4种临床常见的抗真菌药物(氟康唑、两性霉素B、卡泊芬净和5-氟胞嘧啶)和白念珠菌群体感应分子法尼醇对感染后线虫进行治疗,观察线虫存活状态,记录生存率从而评价抗真菌药效。结果 白念珠菌感染线虫后生成菌丝穿破线虫体表造成线虫死亡。氟康唑、卡泊芬净和5-氟胞嘧啶治疗后线虫体内白念珠菌菌丝生长呈现不同程度的抑制状态,线虫生存率有提高且存在量效关系。两性霉素B在该模型中也表现出了明显的体内抗真菌作用,但16 μg/mL、32 μg/mL的高浓度两性霉素B表现出毒性。法尼醇能够抑制线虫体内白念珠菌菌丝形成,但对线虫保护作用较弱。结论 秀丽隐杆线虫-白念珠菌感染模型用于体内抗真菌药效评价方法可靠,并具有通量高、成本低、周期短等优点,值得推广应用。

关键词: 秀丽隐杆线虫, 白念珠菌, 感染模型, 抗真菌药物

Abstract:

Objective To investigate the reliability and stability of Caenorhabditis elegans-Candida albicans infection model in the application of antifungal drug evaluation,and to evaluate the value of this model in antifungal drug development.Method C.albicans was ingested by C.elegans and caused a persistent lethal infection to establish this infection model.Common antifungal drugs includingfuconazole,amphotericin B,caspofungin and 5-fluorocytosine,and farnesol,a quorum sensing molecule secreted by C.albicans,were used to treat the infected nematodes.The survival rate of the nematodes was observed to evaluate the activities of antifugal agents.Results C.albicans infected C.elegans,formed hyphae piercing the cuticle of the nematodes and resulted in the death of the nematodes.Fluconazole,caspofungin and 5-fluorocytosine inhibited the hyphal formation of C.albicans in different degrees in this in vivo model,improving the survival of C.elegans in a dose-dependent manner.Amphotericin B also showed antifungal effect in the C.elegans-C.albicans model,while at high concentrations as 16 or 32 μg/mL,the toxicity of amphotericin B was exhibited.Farnesol inhibited the hyphal formation of C.albicans,but showed weak protection effect to C.elegans.Conclusion The C.elegans-C.albicans infection model is reliable for antifungal drug evaluation.Moreover,this model has high-throughput,low-cost,time-saving properties,and is worthy to be widely used in antifungal drug development.

Key words: Caenorhabditis elegans, Candida albicans, infection model, antifungal drug

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