...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>BMC Infectious Diseases >A peptide fragment from the human COX3 protein disrupts association of Mycobacterium tuberculosis virulence proteins ESAT-6 and CFP10, inhibits mycobacterial growth and mounts protective immune response
【24h】

A peptide fragment from the human COX3 protein disrupts association of Mycobacterium tuberculosis virulence proteins ESAT-6 and CFP10, inhibits mycobacterial growth and mounts protective immune response

机译：来自人类COX3蛋白的肽片段破坏了结核分枝杆菌毒力蛋白ESAT-6和CFP10的结合，抑制了分枝杆菌的生长并增强了保护性免疫应答

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background Tuberculosis (TB) is one of the most prevalent infectious diseases affecting millions worldwide. The currently available anti-TB drugs and vaccines have proved insufficient to contain this scourge, necessitating an urgent need for identification of novel drug targets and therapeutic strategies. The disruption of crucial protein-protein interactions, especially those that are responsible for virulence in Mycobacterium tuberculosis – for example the ESAT-6:CFP10 complex – are a worthy pursuit in this direction. Methods We therefore sought to improvise a method to attenuate M. tuberculosis while retaining the latter’s antigenic properties. We screened peptide libraries for potent ESAT-6 binders capable of dissociating CFP10 from ESAT-6. We assessed the disruption by a peptide named HCL2, of the ESAT-6:CFP10 complex and studied its effects on mycobacterial survival and virulence. Results We found that HCL2, derived from the human cytochrome c oxidase subunit 3 (COX3) protein, disrupts ESAT-6:CFP10 complex, binds ESAT-6 potently, disintegrates bacterial cell wall and inhibits extracellular as well as intracellular mycobacterial growth. In addition, an HCL2 expressing M. tuberculosis strain induces both Th1 and Th17 host protective responses. Conclusions Disruption of ESAT-6:CFP10 association could, therefore, be an alternate method for attenuating M. tuberculosis, and a possible route towards future vaccine generation.
机译：背景结核病（TB）是影响全球数百万人的最流行的传染病之一。事实证明，目前可用的抗结核药物和疫苗不足以遏制这一祸害，因此迫切需要鉴定新的药物靶标和治疗策略。至关重要的蛋白质-蛋白质相互作用的破坏，特别是那些导致结核分枝杆菌中毒力的相互作用，例如ESAT-6：CFP10复合物，是朝着这个方向努力的。方法因此，我们寻求简化结核分枝杆菌同时保留其抗原特性的方法。我们筛选了能够从ESAT-6上解离CFP10的有效ESAT-6结合剂的肽库。我们评估了一种名为HCL2的ESAT-6：CFP10复合物的破坏，并研究了其对分枝杆菌存活和毒力的影响。结果我们发现，源自人类细胞色素C氧化酶亚基3（COX3）蛋白的HCL2破坏ESAT-6：CFP10复合物，有效结合ESAT-6，分解细菌细胞壁并抑制细胞外和细胞内分枝杆菌的生长。此外，表达HCL2的结核分枝杆菌菌株诱导Th1和Th17宿主的保护反应。结论因此，破坏ESAT-6：CFP10关联可能是减毒结核分枝杆菌的另一种方法，并且是未来疫苗生产的可能途径。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号