在卡斯波林治疗期间肠道殖民 Candida glabrata 的进化动态:在脂生物合成中出现临床重要突变
Yasmine Hassoun1, Ariel A Aptekmann1, Mikhail V Keniya1
1Hackensack Meridian Health Center for Discovery and Innovation, Nutley, New Jersey, United States of America.
PLoS pathogens
|September 9, 2024
概括
新兴的抗 echinocandin 抗真菌药物 (如Candida glabrata中的caspofungin) 的耐药性与药物标和其他基因 (如FEN1) 的突变有关,这些基因会影响细胞膜特性.
科学领域:
- 菌类学 菌类学是指菌类学.
- 抗微生物耐药性 抗微生物耐药性
- 医学微生物学 医学微生物学
背景情况:
- 侵袭性真菌感染由于有限的抗真菌选择和药物耐药性增加而造成严重的死亡风险.
- 针对β-葡萄糖合成酶的 Echinocandins 是至关重要的,但面临着日益增长的耐药性,特别是在Candida glabrata.
- 肠道微生物组是抗药性真菌菌株的储存库,但耐药性进化仍然不太清楚.
研究的目的:
- 在肠道殖民模式中研究Candida glabrata对菌素的耐药性的进化机制.
- 为了确定除了药物标突变之外的遗传因素,这些因素有助于 Echinocandin 耐药性.
主要方法:
- 在小鼠的卡斯波辛治疗期间,对C. glabrata的全基因组和安普利康测序.
- 基因操纵 (基因删除) 和C. glabrata突变体的表型分析.
- 高分辨率成像和质谱测量以评估药物膜相互作用.
主要成果:
- 在卡斯波丁治疗期间,C. glabrata的快速遗传多样化,出现了FKS2和FEN1突变.
- 在治疗期间,FEN1突变在肠道中赋予了健身优势,并改变了脂生物合成.
- FEN1突变体显示了与血膜上药物结合性降低相关的 caspofungin 敏感性降低.
- 具有FEN1突变的临床分离物体表现出降低了菌素敏感性.
结论:
- FEN1突变代表了一种新的非药物向机制,有助于C. glabrata的临床 echinocandin 耐药性.
- 了解肠道的耐药性演变对于管理侵入性真菌感染至关重要.
- 这些发现揭示了菌素敏感性的新决定因素,并为打击抗真菌药物耐药性的策略提供了信息.
更多相关视频
相关概念视频
01:28Fungal Phylum Microsporidia
749
Microsporidia are a group of obligate intracellular fungi that were initially classified as protists but were later reclassified based on phylogenetic, molecular, and structural evidence linking them to the Chytridiomycota. These unicellular, non-motile organisms are highly specialized parasites that infect a wide range of animal hosts, including humans. They have evolved extensive genomic and metabolic reductions, making them highly dependent on their hosts for survival.Morphology and Genomic...
749
01:15Antifungal Agents
89
Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to...
89