结核分枝杆菌c-di-GMP代谢相关蛋白的生物化学研究的功能衰退
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摘要
结核病是严重危害人类健康的传染病,由结核分枝杆菌(Mycobacterium tuberculosis,MTB)慢性感染引起,是目前传染病中仅次于艾滋病的第二号杀手。到目前为止,包括研究最深入的结核分枝杆菌菌株H37Rv在内的多个菌株已经被测序,为我们进行结核分枝杆菌的生物学研究,以及发展新的预防治疗结核方法提供了良好的基础。
     环二鸟苷酸(c-di-GMP)是近十余年发现的细菌胞内第二信使,由二分子cGMP通过3′,5?-磷酸二酯键连接而成,在P. aeruginosa、伤寒沙门氏菌(Salmonella typhimurium)等G?细菌和S. aureus等G+细菌中广泛存在。近年来,随着微生物基因组的大规模测序,环二鸟苷酸(c-di-GMP)吸引了越来越多的关注。c-di-GMP在细胞内的水平分别受到含GGDEF结构域(二鸟苷酸环化酶活性)和EAL结构域(磷酸二酯酶活性)蛋白的正向和负向调节,是原核生物中普遍存在的多细胞行为调节因子,通过多种交叉信号网络调控生物膜形成、耐药性、毒力因子表达等生理过程。
Countless millions of people in the world have died from tuberculosis, a chronic infectious disease caused by the tubercle bacillus. The complete genome sequence of the best-characterized Mycobacterium tuberculosis strain, H37Rv, has been determined and analysed in order to improve the understanding of the biology of this slow-growing pathogen and to help finding new prophylactic and therapeutic interventions.
     Bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) has come to the limelight as one of the result of the recent advances in microbial genomics.C-di-GMP is known as a novel global second messenger in bacteria. The GGDEF and EAL domain proteins, which are involved in c-di-GMP synthesis and degradation, respectively, are ubiquitous in bacterial genomes. These proteins affect cell differentiation and multicellular behaviour as well as the interactions between the microorganisms and their eukaryotic hosts.
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