转录调节多宽容和antibiotic-induced histone-like蛋白质Lsr2在结核分枝杆菌的反应。
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Helb Colangeli R, D, Vilcheze C, Hazbon MH,李CG,萨菲H,塞耶斯B, Sardone我,琼斯MB,她RD,彼得森SN,雅各布斯WR Jr Alland D
转录调节多宽容和antibiotic-induced histone-like蛋白质Lsr2在结核分枝杆菌的反应。
公共科学图书馆Pathog。2007年6月;。英镑3(6):共有财产占有一席之地doi: 10.1371 / journal.ppat.0030087。
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17590082 (在PubMed]
- 文摘
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多种药物耐受性是一个关键的表型属性复杂哺乳动物感染结核分枝杆菌的杀菌。先前的研究已经证实iniBAC,一个操纵子,对牛分枝杆菌产生了多种药物耐受性BCG通过一个抖活动有关,是由抗生素引起的异烟肼(INH)、乙胺丁醇(EMB)。一种改进的理解的功能角色antibiotic-induced基因和药物耐受性的规定可能会获得通过研究antibiotic-mediated基因表达调节的因素。一个m . smegmatis应变包含lacZ结核分枝杆菌基因的启动子融合iniBAC (PiniBAC)受到转座子突变。突变体的组成型表达,增加EMB-mediated感应PiniBAC:: lacZ映射到lsr2基因(MSMEG6065),一个小基本未知函数的蛋白质是分枝杆菌中高度保守的。这些突变体有明显变化的菌落形态和生成一个新的极性脂质。互补与多拷贝结核分枝杆菌lsr2 (Rv3597c) PiniBAC表达式返回基线,扭转了观察到的形态和脂质变化,和压抑PiniBAC感应EMB低于控制m . smegmatis压力。的微阵列分析lsr2淘汰赛确认upregulation m . smegmatis iniA并演示了upregulation参与细胞壁的基因和代谢功能。充分循证治疗引起的121 584个基因在野生型m . smegmatis调节(hyperinduced) EMB更高水平的m . smegmatis lsr2淘汰赛。最高度调节基因和基因簇adenine-thymine (AT)丰富的5 '非翻译区。 In M. tuberculosis, overexpression of lsr2 repressed INH-mediated induction of all three iniBAC genes, as well as another annotated pump, efpA. The low molecular weight and basic properties of Lsr2 (pI 10.69) suggested that it was a histone-like protein, although it did not exhibit sequence homology with other proteins in this class. Consistent with other histone-like proteins, Lsr2 bound DNA with a preference for circular DNA, forming large oligomers, inhibited DNase I activity, and introduced a modest degree of supercoiling into relaxed plasmids. Lsr2 also inhibited in vitro transcription and topoisomerase I activity. Lsr2 represents a novel class of histone-like proteins that inhibit a wide variety of DNA-interacting enzymes. Lsr2 appears to regulate several important pathways in mycobacteria by preferentially binding to AT-rich sequences, including genes induced by antibiotics and those associated with inducible multi-drug tolerance. An improved understanding of the role of lsr2 may provide important insights into the mechanisms of action of antibiotics and the way that mycobacteria adapt to stresses such as antibiotic treatment.