Role of whiB6 and kdpDE in the successful multidrug-resistant clone Mycobacterium tuberculosis B0/W148 [kdpDE_RNA-seq]

Among the multidrug-resistant (MDR) clones of Mycobacterium tuberculosis (Mtb) that were epidemiologically particularly successful, the 100-32 MDR Beijing clone, also called B0/W148 clone, has emerged since the early sixties. These B0/W148 strains belonging to the lineage 2 within the global Mtb phylogeny, are the main contributors to the MDR epidemic in Russia and Eastern Europe, and since the USSR's fall, have also propagated to Western Europe. Among the various mutations that were identified as being specific for the MDR B0/W148 clone, we focused on two found in the transcriptional regulators KdpDE and WhiB6 and characterized in a H37Rv strain background the transcriptional profile associated with these mutations and their potential impact on the in vitro and in vivo growth characteristics. Overall design: Gene expression profiling by RNA-seq of the effect induced by the 2-nucleotide deletion in kdpDE of M. tuberculosis H37Rv cultured with and without potassium.

在流行病学传播能力尤为突出的多重耐药（multidrug-resistant, MDR）结核分枝杆菌（Mycobacterium tuberculosis, Mtb）克隆株中，100-32型多重耐药北京株（亦称B0/W148克隆株）自20世纪60年代初开始出现。该B0/W148菌株属于全球结核分枝杆菌系统发育谱系中的2谱系，是俄罗斯与东欧地区多重耐药结核流行的主要致病株；自苏联解体后，该克隆株亦传播至西欧地区。
在已鉴定出的B0/W148多重耐药克隆特异性突变中，我们选取了转录调节因子KdpDE与WhiB6中存在的两种突变进行研究，并在H37Rv菌株背景下，表征了与这些突变相关的转录谱及其对体外、体内生长特性的潜在影响。
总体实验设计：通过RNA测序（RNA-seq）分析结核分枝杆菌H37Rv的kdpDE基因发生2核苷酸缺失后，在添加与不添加钾离子的培养条件下所诱导的基因表达变化。