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首页> 外文期刊>Infection and immunity >Genome-Wide Transposon Mutagenesis Indicates that Mycobacterium marinum Customizes Its Virulence Mechanisms for Survival and Replication in Different Hosts
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Genome-Wide Transposon Mutagenesis Indicates that Mycobacterium marinum Customizes Its Virulence Mechanisms for Survival and Replication in Different Hosts

机译：全基因组转座子诱变表明，海洋分枝杆菌可自定义其毒力机制，以在不同宿主中存活和复制

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The interaction of environmental bacteria with unicellular eukaryotes is generally considered a major driving force for the evolution of intracellular pathogens, allowing them to survive and replicate in phagocytic cells of vertebrate hosts. To test this hypothesis on a genome-wide level, we determined for the intracellular pathogen Mycobacterium marinum whether it uses conserved strategies to exploit host cells from both protozoan and vertebrate origin. Using transposon-directed insertion site sequencing (TraDIS), we determined differences in genetic requirements for survival and replication in phagocytic cells of organisms from different kingdoms. In line with the general hypothesis, we identified a number of general virulence mechanisms, including the type VII protein secretion system ESX-1, biosynthesis of polyketide lipids, and utilization of sterols. However, we were also able to show that M. marinum contains an even larger set of host-specific virulence determinants, including proteins involved in the modification of surface glycolipids and, surprisingly, the auxiliary proteins of the ESX-1 system. Several of these factors were in fact counterproductive in other hosts. Therefore, M. marinum contains different sets of virulence factors that are tailored for specific hosts. Our data imply that although amoebae could function as a training ground for intracellular pathogens, they do not fully prepare pathogens for crossing species barriers.
机译：通常认为环境细菌与单细胞真核生物的相互作用是细胞内病原体进化的主要驱动力，使它们能够在脊椎动物宿主的吞噬细胞中生存和复制。为了在全基因组水平上检验该假设，我们确定了细胞内病原体海洋分枝杆菌是否使用保守的策略来开发原生动物和脊椎动物来源的宿主细胞。使用转座子定向插入位点测序（TraDIS），我们确定了来自不同王国的生物的吞噬细胞中存活和复制的遗传要求的差异。与一般的假设相一致，我们确定了许多一般的毒力机制，包括VII型蛋白分泌系统ESX-1，聚酮脂的生物合成和固醇的利用。但是，我们还能够证明，海藻分枝杆菌含有更多的宿主特异性毒力决定簇，包括参与修饰表面糖脂的蛋白质，以及令人惊讶的是ESX-1系统的辅助蛋白质。这些因素中的一些实际上在其他宿主中适得其反。因此，M。marinum包含针对特定宿主量身定制的不同毒力因子集。我们的数据表明，尽管变形虫可以充当细胞内病原体的训练场，但它们不能为跨物种屏障的病原体充分准备。

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