Research for antifungal mechanisms and therapeutics in refractory deep mycoses

难治性深部真菌病的抗真菌机制和治疗研究

• 批准号: 13670462
• 负责人: MIYAZAKI Yoshitsugu
• 金额: $ 1.66万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670462/
• 关键词: azole; candida albicans; sterol; treatment; virulence; filament; hyphe; fungus; Cryptococcus neoformans; アゾール系抗真菌薬; ERG11; 薬剤感受性; アゾール耐性; 深在性真菌症; クリプトコッカス; 抗真菌薬

We Sterols constituting cell membrane of Candida albicans, one of the most important opportunistic pathogen, play some important roles in causing disease in humans. Here, we created the C. albicans erg3 null mutant to describe effects of sterol dysbolism by defective delta-5, 6-desaturase on azole antifungal susceptibilities, pathogenicity and morphogenesis. The erg3/erg3 strain showed highly azole resistance and ergosta-7, 22-dien-3β-ol accumulated in place of ergosterol was not affected by fluconazole exposure. While, sterol dysbolism by defective delta-5, 6-desaturase increased vulnerability to Sodium dodecyl sulfate (SDS), reduced virulence in a mouse model of systemic candidiasis and suppressed filamentous growth on solid medium and in liquid culture without shaking. Our results are useful for further under standing linkage of multiple signaling pathways for morphogenesis.

白色念珠菌是一种重要的条件致病菌，其分泌物构成白念珠菌的细胞膜，在引起人类疾病中起重要作用。在这里，我们创建了C。白色念珠菌ERG 3无效突变体来描述由缺陷性Δ-5，6-去饱和酶引起的甾醇代谢障碍对唑类抗真菌药敏性、致病性和形态发生的影响。erg 3/erg 3菌株对唑类药物高度耐药，麦角甾-7，22-二烯-3 β-醇替代麦角甾醇的积累不受氟康唑暴露的影响。然而，由缺陷性δ-5，6-去饱和酶引起的固醇代谢障碍增加了对十二烷基硫酸钠（SDS）的脆弱性，降低了系统性念珠菌病小鼠模型中的毒力，并抑制了固体培养基和液体培养物中的丝状生长而不振荡。我们的研究结果有助于进一步了解形态发生的多个信号通路之间的联系。

项目成果

平松啓一: "耐性菌感染症の理論と実際 第2版"医薬ジャーナル社. 281 (2002)

平松敬一：《耐药细菌感染的理论与实践第 2 版》医药杂志 Co., Ltd. 281 (2002)

Kaneko Y.: "Effects of parenterally administered ciprofloxacin in a murine model of pulmonary pseudomonas aeruginosa in fection mimicking ventilator-associated pneumonia"Chemotherapy. 47. 421-429 (2001)

Kaneko Y.：“肠外给予环丙沙星对模拟呼吸机相关肺炎感染的铜绿假单胞菌小鼠模型的影响”化疗。

掛屋 弘: "アゾール系抗真菌薬の標的酵素14α-Demethylaseの点変異の耐性機序への関与"化学療法の領域. 17. 125-132 (2001)

Hiroshi Kakeya：“唑类抗真菌药物的靶酶 14α-去甲基酶的点突变参与耐药机制”Chemotherapy 17. 125-132 (2001)。

Kaneko Y.: "Effects of parenterally administered ciprofloxacin in a murine model of pulmonary pseudomonas aeruginosa infection mimicking ventilator-associated pneumonia"Chemotherapy. 47. 421-429 (2001)

Kaneko Y.：“胃肠外给予环丙沙星对模拟呼吸机相关性肺炎的铜绿假单胞菌感染小鼠模型的影响”化疗。

Hiroshi K: "Effect of mutation in 14 alpha-demthylase on resistant mechanism"Kagakuryoho-no-ryouiki. 17. 125-132 (2001)

Hiroshi K：“14 α-脱甲基酶突变对耐药机制的影响”Kagakuryoho-no-ryouiki。