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分枝杆菌噬菌体整合及裂解的分子机理

Molecular mechanism of the integration and lysis of mycobacteriophage

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【作者】 申严杰; 胡昌华; 王洪海; 谢建平;

【Author】 SHEN Yan-jie~1 HU Chang-hua~1 WANG Hong-hai~2 XIE Jian-ping~(1,2*)(~1Institute of Modern Biopharmaceuticals, School of Life Sciences, Southwest China University, Chongqing 400715, China)(~2State Key Laboratory of Genetic Engineering, School of Life Sciences, Institute of Genetics, Fudan University, Shanghai 200433, China)

【机构】 西南大学生命科学学院现代生物医药研究所,西南大学生命科学学院现代生物医药研究所,复旦大学生命科学学院遗传研究所遗传工程国家重点实验室,西南大学生命科学学院现代生物医药研究所 重庆400715,重庆400715,上海200433,重庆400715; 复旦大学生命科学学院遗传研究所遗传工程国家重点实验室上海200433;

【摘要】 结核病仍旧威胁着全球人类健康,中国是结核病高发国家之一,寻求新的药物和疫苗势在必行。随着对噬菌体研究的深入,分枝杆菌噬菌体成为结核病新型药物发现和药敏实验的研究热点之一。噬菌体进入宿主菌体内,以裂解和溶源两种途径进入循环。以分枝杆菌的溶源性噬菌体为例,综述了分枝杆菌噬菌体整合和裂解分子机理。分枝杆菌溶源性噬菌体的整合需噬菌体基因组的附着位点attachment site(attP),宿主菌分枝杆菌基因组的附着位点attachment site(attB),整合酶integrase(Int)和整合宿主因子integration host factor(mIHF)。部分溶源性噬菌体如Ms6进入裂解循环,复制转录组装成新的子代噬菌体,在裂解素(Lysin)和穿孔素(Holin)的协同作用下裂解宿主菌,释放子代噬菌体。目前国内未见对分枝杆菌噬菌体的研究报道。研究分枝杆菌噬菌体整合及裂解机理对结核病治疗新药开发有一定的启示。

【Abstract】 Tuberculosis remains one of the major threats to public health. China is one of the heavy TB burden countries. Novel drugs and vaccines are urgently needed to combat the increasingly multidrug resistant TB. Mycobacteriophage is one of the hot topic in TB novel drugs discovery and drug susceptibility test. Phages can multiply via two alternative mechanisms: the lytic cycle or the lysogenic cycle. The lytic cycle ends with the lysis and death of the host cell, whereas the host cell remains alive in the lysogenic cycle. Lysogenic mycobacteriophages were intensively studied to elucidate the integration and lysis mechanisms of mycobacteriophage. The integration of mycobacteriophage requires for attP of bacteriopahge genome, attB of Mycobacterium genome, integrase and integration host factor. Some lysogenic phage, eg. mycobacteriophage Ms6,employ lytic cycle, form new phage, lysis host by the cooperation of lysin and holin, and release phages. There is no reports as to the mycobacteriophage unique to China clinical or environmental isolates. Studies on the integration and lysis molecular mechanism of mycobacteriophage might facilitate future new anti-TB drugs development.

【关键词】 分枝杆菌噬菌体; 整合; 裂解;
【Key words】 Mycobacteriophage; Integration; Lysis;
【基金】 国家自然科学基金(30270072);教育部科学技术研究重点项目资助(105146);重庆市科委应用基础项目(2003-8119);西南大学微生物与生化药学学科建设基金资助~~
  • 【文献出处】 微生物学报 ,Acta Microbiologica Sinica , 编辑部邮箱 ,2005年05期
  • 【分类号】R378
  • 【被引频次】3
  • 【下载频次】364
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