Division of Mycobacterial Research, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK.
Mol Microbiol. 2013 Oct;90(1):195-207. doi: 10.1111/mmi.12358. Epub 2013 Aug 23.
In Mycobacterium tuberculosis, the genes Rv1954A-Rv1957 form an operon that includes Rv1955 and Rv1956 which encode the HigB toxin and the HigA antitoxin respectively. We are interested in the role and regulation of this operon, since toxin-antitoxin systems have been suggested to play a part in the formation of persister cells in mycobacteria. To investigate the function of the higBA locus, effects of toxin expression on mycobacterial growth and transcript levels were assessed in M. tuberculosis H37Rv wild type and in an operon deletion background. We show that expression of HigB toxin in the absence of HigA antitoxin arrests growth and causes cell death in M. tuberculosis. We demonstrate HigB expression to reduce the abundance of IdeR and Zur regulated mRNAs and to cleave tmRNA in M. tuberculosis, Escherichia coli and Mycobacterium smegmatis. This study provides the first identification of possible target transcripts of HigB in M. tuberculosis.
在结核分枝杆菌中，基因 Rv1954A-Rv1957 形成一个操纵子，其中包括编码 HigB 毒素和 HigA 抗毒素的 Rv1955 和 Rv1956。我们对这个操纵子的作用和调控很感兴趣，因为毒素-抗毒素系统被认为在分枝杆菌形成持久细胞中起作用。为了研究 higBA 基因座的功能，我们评估了毒素表达对结核分枝杆菌 H37Rv 野生型和操纵子缺失背景中细菌生长和转录水平的影响。我们表明，在没有 HigA 抗毒素的情况下表达 HigB 毒素会导致结核分枝杆菌生长停滞和细胞死亡。我们证明 HigB 表达会减少 IdeR 和 Zur 调控的 mRNA 的丰度，并在结核分枝杆菌、大肠杆菌和耻垢分枝杆菌中切割 tmRNA。这项研究首次鉴定了 HigB 在结核分枝杆菌中的可能靶标转录物。
