cyp51A突变,蛋白质建模和排泄基因表达揭示了多因素的复杂性,以了解阿斯伯吉卢斯部分尼格里醇耐药机制
Pooja Sen1, Mukund Vijay1, Himanshu Kamboj1
1Amity Institute of Biotechnology, Amity University Uttar Pradesh, Sector-125, Noida, Uttar Pradesh, India.
Scientific reports
|March 15, 2024
概括
黑色阿斯伯吉卢斯物种会引起心肌病和肺部阿斯伯吉洛症. 这些真菌的亚醇耐药性不仅仅是由于cyp51A基因突变,而且可能涉及mdr1和mfs基因过度表达.
科学领域:
- 医学真菌学 医学真菌学
- 抗微生物耐药性 抗微生物耐药性
- 分子生物学分子生物学
背景情况:
- 黑色阿斯伯吉卢斯物种是人类感染的重要病因因因子,如奥托米科斯和肺部阿斯伯吉洛斯.
- 关于黑色阿斯伯吉勒斯菌种的抗真菌易感性和耐药性机制的数据有限,特别是那些在环境环境中发现的.
研究的目的:
- 为了确定从印度环境中隔离的黑色阿斯伯吉卢斯物种的醇抗真菌敏感性概况.
- 研究潜在的醇耐药机制,包括cyp51A基因突变和与耐药性相关的基因的表达.
主要方法:
- 从农业土壤样本中分离和识别黑色阿斯伯吉卢斯物种.
- 抗真菌敏感性测试对医疗阿佐尔 (伊特拉可纳,波萨可纳,沃里可纳).
- cyp51A基因测序,蛋白质同质模型和定量基因表达分析 (cyp51A,cyp51B, mdr1, mfs).
主要成果:
- 从174个土壤样本中获得了161个黑色阿斯伯吉卢斯分离物.
- 观察到可变的醇耐药性:11.80%的耐药性是对伊特拉可纳的,3.10%是对波萨可纳的,1.24%是对沃里可纳的.
- 在耐药和易感分离物中发现了非同义的cyp51A突变,对蛋白质结构没有显著影响;然而,在大多数分离物中发现了mdr1和mfs基因的过度表达.
结论:
- 尼格里地区阿斯伯吉路斯的醇耐药性不仅仅归因于cyp51A基因突变或其过度表达.
- 过度表达mdr1和mfs基因可能在赋予这些真菌物种中阿醇耐药性的过程中发挥重要作用.
相关概念视频
01:23Cystic Fibrosis: Pathogenesis
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation, but...
01:15Antifungal Agents
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 cholesterol contributes to...