西亚试剂：Dynamic Persistence of Antibiotic-Stressed Mycobacteria

Dynamic Persistence of Antibiotic-Stressed Mycobacteria

Yuichi Wakamoto1,*,†, Neeraj Dhar1,*, Remy Chait2,‡, Katrin Schneider1, François Signorino-Gelo1,Stanislas Leibler2,3, John D. McKinney1,§

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.

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