Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14583, USA.
Mol Microbiol. 2011 May;80(3):678-94. doi: 10.1111/j.1365-2958.2011.07601.x. Epub 2011 Mar 14.
Following phagocytosis by macrophages, Mycobacterium tuberculosis (Mtb) senses the intracellular environment and remodels its gene expression for growth in the phagosome. We have identified an acid and phagosome regulated (aprABC) locus that is unique to the Mtb complex and whose gene expression is induced during growth in acidic environments in vitro and in macrophages. Using the aprA promoter, we generated a strain that exhibits high levels of inducible fluorescence in response to growth in acidic medium in vitro and in macrophages. aprABC expression is dependent on the two-component regulator phoPR, linking phoPR signalling to pH sensing. Deletion of the aprABC locus causes defects in gene expression that impact aggregation, intracellular growth, and the relative levels of storage and cell wall lipids. We propose a model where phoPR senses the acidic pH of the phagosome and induces aprABC expression to fine-tune processes unique for intracellular adaptation of Mtb complex bacteria.
分枝杆菌（Mycobacterium tuberculosis，Mtb）被巨噬细胞吞噬后，会感知细胞内环境，并重塑其基因表达，以适应吞噬体中的生长。我们已经鉴定出一个独特的分枝杆菌复合体的酸性和吞噬体调节（aprABC）基因座，其基因表达在体外酸性环境中和巨噬细胞内的生长过程中被诱导。利用 aprA 启动子，我们构建了一株在体外酸性培养基和巨噬细胞中生长时，能够高水平诱导荧光的菌株。aprABC 的表达依赖于双组分调控因子 phoPR，将 phoPR 信号与 pH 感应联系起来。aprABC 基因座的缺失导致基因表达缺陷，影响聚集、细胞内生长以及储存和细胞壁脂质的相对水平。我们提出了一个模型，即 phoPR 感知吞噬体的酸性 pH，并诱导 aprABC 的表达，以微调分枝杆菌复合体细菌适应细胞内环境的独特过程。
