科学家揭示结核菌耐药性奥秘

海内知己

High Functional Diversity in Mycobacterium tuberculosis Driven by Genetic Drift and Human Demography

Tuberculosis remains a worldwide public health emergency. The emergence of drug-resistant forms of tuberculosis in many parts of the world is threatening to make this important human disease incurable. Even though many resources are being invested into the development of new tuberculosis control tools, we still do not know the extent of genetic diversity in tuberculosis bacteria, nor do we understand the evolutionary forces that shape this diversity. To address these questions, we studied a large collection of human tuberculosis strains using DNA sequencing. We found that strains originating in different parts of the world are more genetically diverse than previously recognized. Our results also suggest that much of this diversity has functional consequences and could affect the efficacy of new tuberculosis diagnostics, drugs, and vaccines. Furthermore, we found that the global diversity in tuberculosis strains can be linked to the ancient human migrations out of Africa, as well as to more recent movements that followed the increases of human populations in Europe, India, and China during the past few hundred years. Taken together, our findings suggest that the evolutionary characteristics of tuberculosis bacteria could synergize with the effects of increasing globalization and human travel to enhance the global spread of drug-resistant tuberculosis

科学家发现了结核菌的遗传秘密，这个秘密对于结核菌的多药耐药性的急剧增长可能有贡献。

这项研究是对全球结核菌多样性的首个调查，它发现了这些细菌比此前认为的更加具有遗传多样性。

这些科学家检查了结核病的致病菌结核分枝杆菌的99种菌株。他们还检查了9种只感染动物的菌株。

让他们感到震惊的是，他们发现人类结核菌菌株之间的遗传多样性要远远高于动物菌株，这与此前认为的所有人类结核菌菌株基本相同的观念相抵触。

“我们发现结核分枝杆菌不像我们此前认为的那样相同，”该研究的作者之一、曾在美国系统生物学研究所工作、如今在英国国立医学研究所的Sebastien Gagneux说。

这组科学家还发现这种细菌的遗传选择率低。它们通过一种称为遗传漂变（genetic drift）的过程积累它们的DNA的突变，而且几乎没有抑制这些突变的选择压力。由于这个原因，带来耐药性的突变不会从基因库中消失，而会持续存在于种群中。

通常，带来耐药性的遗传突变会对细菌造成损害，因为它们的获得是以细菌的其他机制被削弱为代价的。细菌的这种另外的机制抑制着它们的耐药性。但是这对于结核病并非如此。

这组科学家的研究发表在了12月16日出版的《公共科学图书馆·生物学》（PLoS Biology）杂志上，他们发现人类结核分枝杆菌可以分为两个独特的群体：仅见于西非以及印度洋沿岸的“古代”菌株，以及在欧洲、美洲、东亚、东非和印度占主流的“现代”世系。

这组科学家发现了遗传和地理距离之间的相关性，这提示了古代人类走出非洲的陆地移民路径把结核病向北携带到了欧洲，向东携带到了印度洋附近，但是现代菌株沿着海路迁移回了非洲。

“有可能古代菌株被现代菌株排挤掉了，例如，在加勒比地区，尽管古代菌株因为奴隶贸易而到达那里，现在那里只有现代菌株，” Gagneux告诉本网站说。

这组科学家说，由于这一因素，再加上今天的全球范围的旅行，结核病控制项目的设计者应该把地理上的菌株多样性考虑进去。

转自丁香园:ok