来自来自瑞士洛桑联邦理工大学、美国洛克菲勒大学、普林斯顿高等研究院的研究人员发现先进行分裂后脉冲性表达过氧化氢-过氧化物酶(KatG)的细菌能在抗生素药物异烟肼(INH)的处理下幸存。这项研究揭示了抗生素处理下细菌新的存活机制。

-2013年1月4日《科学》

中文翻译


【题目】抗生素胁迫下分支杆菌的持久性生存动力学

【译文】对同基因型的细菌种群施加杀灭性抗生素处理,通常还是难以杀死所有的细菌,总有一小部分生命力极强的细菌幸存。以往观点认为,抗生素部分性杀伤作用是因为细菌种群中存在很少分裂或不分裂的持留菌。借助微流控培养技术和延时显微成像技术,本研究发现耻垢分枝杆菌(Mycobacterium smegmatis)在抗结核药物异烟肼(INH)的存在下,仍然能持续繁殖。尽管在这些研究中,细菌种群持久性生存的特点都表现为细菌数量稳定,细菌种群看似稳定,但实际上是细菌繁殖和死亡达到动态平衡的结果。细菌随机脉冲性地表达过氧化氢-过氧化物酶(KatG),KatG能够激活INH,激活的INH能够杀死细菌,因此KatG与细菌的生长呈负相关。这些行为可能反映出细菌的表观遗传效应,因为在同基因型细菌之间,脉冲性产生的KatG与细菌死亡有关。抗生素处理下幸存的细菌个体,其特点表现为产生稀少的KatG脉冲,使得这些细菌在药物暴露时间延长的条件下获得无响应适应能力。

英文原稿


[Title]: Dynamic Persistence of Antibiotic-Stressed Mycobacteria

[Authors]: Yuichi Wakamoto, Neeraj Dhar, Remy Chait, Katrin Schneider, François Signorino-Gelo, Stanislas Leibler, and John D. McKinney

[Abstract]: Exposure of an isogenic bacterial population to a cidal antibiotic typically fails to eliminate a small fraction of refractory cells. Historically, fractional killing has been attributed to infrequently dividing or nondividing “persisters.” Using microfluidic cultures and time-lapse microscopy, we found that Mycobacterium smegmatis persists by dividing in the presence of the drug isoniazid (INH). Although persistence in these studies was characterized by stable numbers of cells, this apparent stability was actually a dynamic state of balanced division and death. Single cells expressed catalase-peroxidase (KatG), which activates INH, in stochastic pulses that were negatively correlated with cell survival. These behaviors may reflect epigenetic effects, because KatG pulsing and death were correlated between sibling cells. Selection of lineages characterized by infrequent KatG pulsing could allow nonresponsive adaptation during prolonged drug exposure.

原文地址

http://www.sciencemag.org/content/339/6115/91.short

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