A replication clock for Mycobacterium tuberculosis.
A replication clock for Mycobacterium tuberculosis.
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作者：
很少有工具可以评估感染期间慢性病原体的复制。这对于了解潜伏性结核病来说是一个相当大的障碍，开发新疗法的努力通常假设细菌在潜伏期复制非常缓慢或不复制。为了监测结核分枝杆菌在宿主内的复制，我们利用了一种不稳定的质粒，该质粒在没有抗生素选择的情况下以稳定、可量化的速率从分裂细胞中丢失。通过应用数学模型，我们计算了小鼠感染期间的细菌生长和死亡率。我们表明，在慢性感染过程中，累积的细菌负荷（计算小鼠肺部遇到的活的、死的和去除的微生物总数）远远高于菌落形成单位的估计值。我们的数据表明，结核分枝杆菌在小鼠慢性感染过程中不断复制，并受到宿主免疫系统的抑制。这种方法还可能揭示其他慢性病原体的复制动态。
Few tools exist to assess replication of chronic pathogens during infection. This has been a considerable barrier to understanding latent tuberculosis, and efforts to develop new therapies generally assume that the bacteria are very slowly replicating or nonreplicating during latency. To monitor Mycobacterium tuberculosis replication within hosts, we exploit an unstable plasmid that is lost at a steady, quantifiable rate from dividing cells in the absence of antibiotic selection. By applying a mathematical model, we calculate bacterial growth and death rates during infection of mice. We show that during chronic infection the cumulative bacterial burden—enumerating total live, dead and removed organisms encountered by the mouse lung—is substantially higher than estimates from colony forming units. Our data show that M. tuberculosis replicates throughout the course of chronic infection of mice and is restrained by the host immune system. This approach may also shed light on the replication dynamics of other chronic pathogens.
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影响因子：
4.9
作者：
Lenaerts, AJ;Gruppo, V;Orme, IM
通讯作者：
Orme, IM
影响因子：
2.9
作者：
Meijer, Annemarie H.;van der Sar, Astrid M.;Spaink, Herman P.
通讯作者：
Spaink, Herman P.
T细胞亚群在小鼠中的肺结核感染的免疫和免疫病理学中的相对重要性。
影响因子：
15.3
作者：
Mogues, T;Goodrich, M E;Ryan, L;LaCourse, R;North, R J
通讯作者：
North, R J
影响因子：
3.2
作者：
Smeulders, MJ;Keer, J;Williams, HD
通讯作者：
Williams, HD
DOI：
10.1016/s0962-8479(97)90016-2
发表时间：
1997-01-01
期刊：
TUBERCLE AND LUNG DISEASE
影响因子：
--
作者：
Rhoades, ER;Frank, AA;Orme, IM
通讯作者：
Orme, IM