诊断学理论与实践

诊断学理论与实践 ›› 2021, Vol. 20 ›› Issue (04): 356-361.doi: 10.16150/j.1671-2870.2021.04.005

• 论著 • 上一篇    下一篇

新型咪唑类药物2-咪唑-2,4-戊二烯酮19和44对白念珠菌抗菌效果和作用机制初步研究

陈华1, 刘锦燕1, 李文静1,2, 赵珺涛1,2, 项明洁1,2()   

  1. 1.上海交通大学医学院附属瑞金医院卢湾分院放免检验科,上海 200020
    2.上海交通大学医学院附属瑞金医院检验科,上海 200025
  • 收稿日期:2019-08-26 出版日期:2021-08-25 发布日期:2022-06-28
  • 通讯作者: 项明洁 E-mail:mjxiang123456@126.com
  • 基金资助:
    国家自然科学基金项目(81871706);上海市卫计委课题(201840227);上海市卫计委课题(201740069);上海市黄浦区卫计委课题(HKM201702);上海市重点专科配套课题(ZK2012A21)

Preliminary study of antifungal effect and mechanism of novel imidazoles 2-imidazole-2, 4-pentadienone 19 and 44 on Candida albicans

CHEN Hua1, LIU Jinyan1, LI Wenjing1,2, ZHAO Juntao1,2, XIANG Mingjie1,2()   

  1. 1. Radioimmunology and Clinical Laboratory, Luwan Branch, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine,Shanghai 200020, China
    2. Department of Clinical Laboratory, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Received:2019-08-26 Online:2021-08-25 Published:2022-06-28
  • Contact: XIANG Mingjie E-mail:mjxiang123456@126.com

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摘要：

目的：测定新型咪唑类药物2-咪唑-2,4-戊二烯酮（以下简称新型药物）19和44对白念珠菌的抑制作用,并初步探讨其抑制白念珠菌的机制。 方法：以氟康唑为对照组,采用体外药敏试验（氟康唑、新型药物19和44的药物浓度均设0.25~128.00 μg/mL的倍增梯度）、菌丝抑制试验（氟康唑、新型药物19和44的浓度均设0、2.00、8.00、16.00 μg/mL梯度）以及结晶紫染色细胞计数实验（氟康唑、新型药物19和44的浓度均设2.00、8.00、16.00、64.00 μg/mL浓度梯度）,评估新型药物19和44对白念珠菌标准菌株SC5314、ATCC90028及临床分离株的抗菌效果。采用透射电镜观察在新型药物19（0.50 μg/mL）和44（2.00 μg/mL）作用下的白念珠菌细胞膜和细胞器形态变化。 结果：体外药敏试验结果显示,氟康唑、新型药物19、新型药物44对白念珠菌SC5314的最小抑菌浓度（minimal inhibit concentration, MIC）分别为1.00、0.50、2.00 μg/mL。白念珠菌临床分离株21897、210和141均为氟康唑耐药株（MIC>128.00 μg/mL）,新型药物44对这些菌株的MIC分别为8.00 μg/mL、16.00 μg/mL和16.00 μg/mL。菌丝抑制试验结果显示,在分别含有氟康唑、新型药物19、新型药物44的培养液中,白念珠菌SC5314的菌丝生长均被明显抑制。透射电镜观察结果显示,新型药物19、44可使SC5314的细胞膜出现厚薄不均且质地粗糙的变化,与无药对照组间结构差异明显。 结论：新型药物19和44对白念珠菌有较强的抑制作用,可改变白念珠菌细胞膜的结构。

关键词: 白念珠菌, 2-咪唑-2,4-戊二烯酮, 抑制作用, 细胞膜, 耐药

Abstract:

Objective: To detect the antifungal effect of the novel imidazoles 2-imidazole-2, 4-pentadienone 19 and 44 on Candida albicans, and explore the mechanism of the antifungal effect preliminarily. Methods: The inhibitory effects of 2-imidazole-2, 4-pentadienone 19 and 44 on Candida albicans standard strains SC5314, ATCC90028 and clinical isolates were observed through susceptibility test in vitro (the concentration gradients of fluconazole, 2-imidazole-2, 4-pentadienone 19 and 44 were all set in 0.25-128.00 μg/mL), hyphal inhibition test (the concentration gradients of fluconazole, 2-imidazole-2, 4-pentadienone 19 and 44 were all set in 0, 2.00, 8.00, 16.00 μg/mL) and crystal violet staining cell coun-ting test (the concentration gradients of fluconazole, 2-imidazole-2, 4-pentadienone 19 and 44 were all set 2.00, 8.00, 16.00, 64.00 μg/mL). The morphological changes of membrane and organelles in Candida albicans were observed by transmission electron microscopy when they were cultured with 2-imidazole-2, 4-pentadienone 19 (0.50 μg/mL) and 44 (2.00 μg/mL). Results: The susceptibility test in vitro showed that the minimal inhibitory concentrations (MIC) of fluconazole, new drug 19, and new drug 44 on Candida albicans SC5314 were 1.00, 0.50, and 2.00 μg/mL, respectively. The clinical isolates of Candida albicans 21897, 210 and 141 were all fluconazole-resistant strains (MIC>128.00 μg/mL). The MICs of new drug 19 on three type isolates were 64.00 μg/mL,> 128.00 μg/mL and 64.00 μg/mL, and the MICs of new drug 44 on them were 8.00 μg/mL, 16.00 μg/mL and 16.00 μg/mL, respectively. The mycelial inhibition experiment showed that the mycelial growth of Candida albicans SC5314 was significantly inhibited in the culture medium containing fluconazole and the novel drugs 19 and 44, and the higher the drug concentration (≤64.00 μg/mL). The inhibitory effects of new drugs 19 and 44 were better than fluconazole as the drug concentrations were 8.00 μg/ml or 64.00 μg/mL. Transmission electron microscopy showed that fluconazole and the novel drugs 19 and 44 led the cell membrane of SC5314 to become uneven and coarse in texture, which was obviously different from that of drug-free control. Conclusions: The new imidazoles 2-imidazole-2, 4-pentadienone 19 and 44 show strong inhibitory effects on Candida albicans by changing the structure of cell membrane.

Key words: Candidaalbicans, New imidazole drugs, Inhibition, Cell membrane

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