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聚焦于分子生物学视角下的结核病

[Tuberculosis focused through the molecular biology zoom].

作者信息

Barrera L

机构信息

Instituto Nacional de Enfermedades Infecciosas ANLIS Dr. Carlos G. Malbrán, Buenos Aires.

出版信息

Medicina (B Aires). 2000;60(1):17-25.

PMID:10835696
Abstract

The sequence of Mycobacterium tuberculosis genome set up a process of systematic research and improved the understanding of the microorganism biology, albeit the clues of its virulence and pathogenicity still remain rather cryptic. Genetic engineering did not succeed in designing more effective or convenient tools to accomplish the control of tuberculosis. Neither the bacillus variants created by mutagenesis and recombination nor the microorganism subunits (antigens, DNA) proved to be significantly better than the BCG vaccine as immunogens. Likewise, the search for novel bacterial targets and more active antibiotics has been unfruitful thus far, even though some advance in drugs formula or delivery systems is in progress. Conversely, new and ingenious instruments have been developed to optimize the epidemiological tracing and diagnosis of the disease. The finding of strain molecular markers consolidated the investigation of tuberculosis spread and revealed the expansion and prevalence of certain lineages of the bacillus in some ecological niches. Molecular methods are specific to immediately characterize the bacilli detected by microscopy or culture which resulted in rapid diagnosis build-up. This improvement is decisive for immunodepressed patients and those affected by multidrug-resistant tuberculosis. To be meaningful and precise the results produced by molecular investigations must be properly backed up by conventional microbiology, pathology and epidemiology.

摘要

结核分枝杆菌基因组序列开启了系统研究进程,增进了对该微生物生物学特性的理解,尽管其毒力和致病性线索仍相当隐晦。基因工程未能成功设计出更有效或便捷的工具来实现结核病防控。无论是通过诱变和重组产生的杆菌变体,还是微生物亚单位(抗原、DNA),作为免疫原都未被证明比卡介苗显著更优。同样,迄今为止,寻找新的细菌靶点和更有效的抗生素也未取得成果,尽管在药物配方或递送系统方面有一些进展。相反,已开发出新颖且精巧的工具来优化该疾病的流行病学追踪和诊断。菌株分子标记的发现巩固了对结核病传播的研究,并揭示了杆菌某些谱系在一些生态位中的扩张和流行情况。分子方法能够特异性地立即鉴定通过显微镜检查或培养检测到的杆菌,从而实现快速诊断。这一改进对免疫抑制患者和耐多药结核病患者至关重要。为使分子研究产生的结果有意义且精确,必须得到传统微生物学、病理学和流行病学的适当支持。

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