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Juliana Rizzo^1,2, Adèle Trottier¹, Frédérique Moyrand¹

¹Institut Pasteur, Université Paris Cité, Unité Biologie des ARN des Pathogènes Fongiques , Paris, France.

|June 13, 2023

概括

克里普托可克新型菌通过控制细胞外囊泡 (EV) 生产来调节抗真菌耐药性,而不是药物标. 降低EV产量与可纳耐药性相关,这表明EV是关键的防御机制.

科学领域:

菌类学菌类学是指菌类学.
细胞生物学细胞生物学
抗微生物耐药性抗微生物耐药性

背景情况:

菌中富可纳 (FLC) 耐药性往往涉及药物向修改或排泄升调.
新出现的证据表明,囊泡性贩运和抗真菌药物耐药性之间存在联系.
细胞外囊泡 (EVs) 参与真菌群体相互作用,但它们在药物耐药性中的作用尚不清楚.

研究的目的:

为了确定 *Cryptococcus neoformans* 中细胞外囊泡 (EV) 生物发生的调节者,这些调节者会影响流可纳 (FLC) 耐药性.
调查电动汽车生产与FLC电阻机制之间的关系.
探索EV调制作为一种新型抗真菌耐药性战略的潜力.

主要方法:

在C. neoformans*中发现EV生物发生的新型调节剂.
分析转录因子Hap2对细胞固醇特征和FLC耐药性的影响.
在低抑制FLC度下以及在FLC耐药突变物和临床分离物中评估EV生产.
在FLC电阻逆转时EV生产变化的评估.

主要成果:

确定了影响*C. neoformans*中FLC耐药性的EV生物发生的新型调节剂.
转录因子Hap2会影响细胞的固醇特征,但不会影响药物标或排泄的表达.
抑制性FLC度,自发性耐药性获得和临床FLC耐药性与降低的EV产生有关.
FLC电阻的逆转与增加的EV产量相关.

结论:

细胞可能利用EV生产调节作为对抗真菌攻击的主要防御,独立于药物标调节.
在 *C. neoformans* 中,EV 生产和醇耐药性是共同调节的,正如在各种菌株和临床隔离物中观察到的.
调节EV生产代表了这种病原体抗真菌药物耐药性的新机制.

关键词:

这是Cryptococcus neoformans的新型菌.抗微生物耐药性抗微生物耐药性细胞外囊泡中的细胞外囊泡.弗卢科纳尔 (Fluconazole) 是一种转录因子的转录因子

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