鉴定MRSA突变体中赋予泰迪索利德耐药性的遗传突变
Nesma B Goda1, Amira M El-Ganiny2, Tharwat R El-Khamissy3
1Microbiology and Immunology Department, Faculty of Pharmacy, Egyptian Russian University, Badr, Egypt. nesma-barbary@eru.edu.eg.
概括
在MRSA中,rplC基因的新突变可能会导致对linezolid和tedizolid的交叉耐药性. 这些发现还揭示了由特定突变调解的佐利丁和利法之间的交叉耐药性.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 抗微生物耐药性 抗微生物耐药性
背景情况:
- 之前的研究已经排除了对泰迪索利德耐药性的基因介导机制.
- 了解突变介导机制对于打击抗生素耐药性至关重要.
研究的目的:
- 调查突变介导的机制,使得甲基西林耐药黄金葡萄球菌 (MRSA) 中的oxazolidinone交叉抗性.
- 为了确定与泰迪索利德耐药性相关的特定突变.
- 探索 rpoB 突变在 tedizolid 耐药性获得中的作用.
主要方法:
- 在实验室中从五个cfr-负临床分离物中选择了对线胺耐药MRSA突变物.
- 在已发展的突变体中评估泰迪索利德交叉耐药性.
- 全基因组测序,变异调用和注释以识别突变.
- 对突变与观察到的耐药性相关性的分析.
主要成果:
- 在rpoB (RNA聚合酶β子单元) 和rplC (50S核糖体蛋白L3) 中发现的突变与tedizolid耐药性相关.
- 检测到mepB基因突变,可能导致linezolid耐药性.
- 通过RRDR中的单个氨基酸替代,观察到佐利丁和里法之间的交叉耐药性.
结论:
- 在50S核糖体蛋白L3中的Gly152Asp突变是首次报告的突变,它仅对linezolid和tedizolid产生交叉耐药性.
- 在RRDR中单个氨基酸替代可以导致oxazolidinones和rifampin之间的交叉电阻.
- mepB突变表明一个独立于MepR的机制调节了mepRAB操作子,有助于获得的linezolid耐药性.
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