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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Genome-wide requirements for Mycobacterium tuberculosis adaptation and survival in macrophages
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Genome-wide requirements for Mycobacterium tuberculosis adaptation and survival in macrophages

机译：全基因组结核分枝杆菌适应性和巨噬细胞生存的要求

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摘要

Macrophages are central to host defense against microbes, but intracellular pathogens have evolved to evade their antimicrobial functions. Mycobacterium tuberculosis (MTB) has successfully exploited macrophages as its primary niche in vivo, but the bacterial genome-wide requirements that promote its intracellular survival remain undefined. Here we comprehensively identify the MTB genes required for survival by screening for transposon mutants that fail to grow within primary macrophages. We identify mutants showing decreased growth in macrophage environments that model stages of the host immune response. By systematically analyzing several biologically relevant data sets, we have been able to identify putative pathways that could not be predicted by genome organization alone. In one example, phosphate transport, requiring physically unlinked genes, was found to be critical for MTB growth in macrophages and important for establishing persistent infection in lungs. Remarkably, the majority of MTB genes found by this analysis to be required for survival are constitutively expressed rather than regulated by macrophages, revealing the host-adapted lifestyle of an evolutionarily selected intracellular pathogen.
机译：巨噬细胞是宿主抵抗微生物的关键，但是细胞内病原体已经进化出逃避其抗微生物功能的能力。结核分枝杆菌（MTB）已成功利用巨噬细胞作为其体内的主要生物位，但促进其细胞内存活的细菌全基因组要求仍然不确定。在这里，我们通过筛选未能在原代巨噬细胞内生长的转座子突变体，全面鉴定了生存所需的MTB基因。我们鉴定出突变体，其在模拟宿主免疫反应阶段的巨噬细胞环境中显示出降低的生长。通过系统地分析几个生物学上相关的数据集，我们已经能够确定单独的基因组组织无法预测的推定途径。在一个例子中，发现需要物理上不相关的基因的磷酸盐运输对巨噬细胞中MTB的生长至关重要，对建立肺部持续感染也很重要。值得注意的是，通过该分析发现存活所需的大多数MTB基因是组成型表达的，而不是由巨噬细胞调控的，这揭示了宿主进化的细胞内病原体的适应性生活方式。

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