Chakhaiyar Prachee, Hasnain Seyed E
Laboratory of Molecular and Cellular Biology, Centre for DNA Fingerprinting and Diagnostics, Nacharam, Hyderabad 500 076, India.
Med Princ Pract. 2004 Jul-Aug;13(4):177-84. doi: 10.1159/000078312.
The identification of Mycobacterium tuberculosis by Robert Koch in 1882 as the causative agent of tuberculosis, the release of the drug rifampicin in 1970 and the sequencing of the M. tuberculosis genome in 1998 are three major events that have revolutionized tuberculosis research. In spite of these breakthroughs, the continued status of tuberculosis as the largest killer amongst infectious diseases is an issue of major concern. Although directly observed short course chemotherapy exists to treat the disease, the emergence of drug-resistant strains has severely threatened the efficacy of the treatment. The recent sequencing of the M. tuberculosis genome holds promise for the development of new vaccines and the design of new drugs. This is all the more possible when the information from the genome sequence is combined with proteomics and structural and functional genomics. Such an integrated approach has led to the birth of a new field of research christened 'postgenomics' that holds substantial promise for the identification of novel drug targets and the potential to aid the development of new chemotherapeutic compounds to treat tuberculosis. The challenge before the scientific community therefore lies in elucidation of the wealth of information provided by the genome sequence and its translation into the design of novel therapies for the disease. All the major developments in the field of tuberculosis research after the sequencing of the M. tuberculosis genome will be discussed in this review.
1882年罗伯特·科赫鉴定出结核分枝杆菌是结核病的病原体,1970年利福平药物的问世以及1998年结核分枝杆菌基因组的测序,是彻底改变结核病研究的三大重要事件。尽管有这些突破,但结核病作为传染病中最大杀手的持续现状仍是一个重大关切问题。虽然存在直接观察短程化疗来治疗该疾病,但耐药菌株的出现严重威胁了治疗效果。结核分枝杆菌基因组的最新测序为新疫苗的开发和新药的设计带来了希望。当基因组序列信息与蛋白质组学以及结构和功能基因组学相结合时,这种可能性就更大了。这种综合方法催生了一个名为“后基因组学”的新研究领域,该领域在鉴定新的药物靶点以及帮助开发治疗结核病的新型化疗化合物方面具有巨大潜力。因此,科学界面临的挑战在于阐明基因组序列提供的丰富信息,并将其转化为针对该疾病的新型疗法设计。本文将讨论结核分枝杆菌基因组测序后结核病研究领域的所有重大进展。