Disclosure of Selective Advantages in the "modern" Sublineage of the Mycobacterium tuberculosis Beijing Genotype Family by Quantitative Proteomics
Disclosure of Selective Advantages in the "modern" Sublineage of the Mycobacterium tuberculosis Beijing Genotype Family by Quantitative Proteomics
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DOI：
10.1074/mcp.m114.038380
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发表时间：
2014-10-01
影响因子：
7
通讯作者：
van Soolingen, Dick
中科院分区：
文献类型：
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作者：
de Keijzer, Jeroen;de Haas, Petra E.;van Soolingen, Dick
结核分枝杆菌北京基因型由更古老（非典型）和现代（典型）新兴亚系组成，是最流行和遗传保守的基因型家族之一，通常与多重耐药性相关。在这项研究中，我们采用 2D-LC-FTICR MS 方法，结合胰蛋白酶肽二甲基化，系统地比较古代和现代北京菌株的蛋白质丰度水平，并确定可能与现代亚系成功传播相关的差异。该数据可通过 ProteomeXchange 使用标识符 PXD000931 获得。尽管两个亚系的蛋白质丰度比高度一致，但我们发现两个亚系之间有四种蛋白质受到差异调节，这可以解释现代北京菌株的适应性明显增强。这些蛋白质是； Rv0450c/MmpL4、Rv1269c、Rv3137 和 Rv3283/sseA。对 29 个北京毒株中这些蛋白的转录和功能分析表明，Rv0450c/MmpL4 的 mRNA 水平在现代北京毒株中显着较高，而我们还提供了证据表明 Rv3283/sseA 在现代北京毒株中的丰度较低。我们的研究结果为现代北京亚系的毒力增强和成功提供了可能的解释。此外，在已建立的 1817 个蛋白质数据集中，我们证明了北京菌株蛋白质组中预先存在的几种可能是独特的抗生素外排泵。这可能反映出北京菌株逃避抗结核药物暴露的能力增强。
The Mycobacterium tuberculosis Beijing genotype, consisting of the more ancient (atypical) and modern (typical) emerging sublineage, is one of the most prevalent and genetically conserved genotype families and has often been associated with multidrug resistance. In this study, we employed a 2D-LC-FTICR MS approach, combined with dimethylation of tryptic peptides, to systematically compare protein abundance levels of ancient and modern Beijing strains and identify differences that could be associated with successful spread of the modern sublineage. The data is available via ProteomeXchange using the identifier PXD000931. Despite the highly uniform protein abundance ratios in both sublineages, we identified four proteins as differentially regulated between both sublineages, which could explain the apparent increased adaptation of the modern Beijing strains. These proteins are; Rv0450c/MmpL4, Rv1269c, Rv3137, and Rv3283/sseA. Transcriptional and functional analysis of these proteins in a large cohort of 29 Beijing strains showed that the mRNA levels of Rv0450c/MmpL4 are significantly higher in modern Beijing strains, whereas we also provide evidence that Rv3283/sseA is less abundant in the modern Beijing sublineage. Our findings provide a possible explanation for the increased virulence and success of the modern Beijing sublineage. In addition, in the established dataset of 1817 proteins, we demonstrate the pre-existence of several, possibly unique, antibiotic efflux pumps in the proteome of the Beijing strains. This may reflect an increased ability of Beijing strains to escape exposure to antituberculosis drugs.