Cell population heterogeneity in Mycobacterium tuberculosis H37Rv
Cell population heterogeneity in Mycobacterium tuberculosis H37Rv
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DOI：
10.1016/j.tube.2008.03.005
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发表时间：
2008-11-01
期刊：
影响因子：
3.2
通讯作者：
Gibert, Isidre
中科院分区：
文献类型：
--
作者：
Andreu, Nuria;Gibert, Isidre
实验室菌株H37Rv是结核分枝杆菌研究中最常用的菌株之一。尽管该菌株表面上是稳定的，但缺乏毒力因子的选择压力可能会导致减毒突变株的体外积累。为了验证这一假设，我们对从传代培养的结核分枝杆菌H37Rv和从非传代培养的冰冻菌种分离的单个克隆进行了系统分析。首先，我们研究了两个毒力指标：中性红染色和邻苯二甲酸二菌酯(PDIMs)含量。我们发现，H37Rv形成了一个包含野生型细胞以及中性红和PDIM突变体的混合群体。然后，我们通过微阵列分析比较了3个分离克隆(表现出不同表型)和未传代群体的整体基因表达。这一转录获利证实，尽管存在中性红和PDIM表型，但存在显著的异质性。这些结果强烈表明，在推断体外培养的结核分枝杆菌H37Rv的数据时必须非常谨慎，研究几个独立的克隆将是谨慎的，以获得有效的结论。为此，中性红和PDIM表型可能是不受欢迎的异质性的有用指示器。(C)2008爱思唯尔有限公司。保留所有权利。
The laboratory strain H37Rv represents one of the most commonly used strains in the study of Mycobacterium tuberculosis. Despite the apparent stability of the strain, the absence of a selective pressure for virulence factors could lead to the in vitro accumulation of attenuated mutants. To assess this hypothesis, we performed a systematic analysis of individual clones isolated from subcultured M. tuberculosis H37Rv and from a non-subcultured frozen stock. First, we studied two virulence indicators: neutral red staining and content of phthiocerol dimyco-cerosates (PDIMs). We found that H37Rv formed a mixed population containing wild-type cells, as well as neutral red and PDIM mutants. Then, we compared the global gene expression of 3 isolated clones (which displayed various phenotypes) and the non-subcultured stock, by micro-array analysis. This transcriptional profiting confirmed that a significant heterogeneity existed despite, and in addition to, the neutral red and PDIM phenotypes. These results strongly suggest that great caution must be taken in extrapolating data obtained with M. tuberculosis H37Rv grown in vitro, and it would be prudent to study several independent clones to obtain valid conclusions. For this purpose, the neutral red and PDIM phenotypes might be useful indicators of undesired heterogeneity. (C) 2008 Elsevier Ltd. All rights reserved.