Dynamic persistence of antibiotic-stressed mycobacteria Journal Article

Author(s): Wakamoto, Yurichi; Dhar, Neraaj; Chait, Remy; Schneider, Katrin; Signorino Gelo, François; Leibler, Stanislas; McKinney, John D
Article Title: Dynamic persistence of antibiotic-stressed mycobacteria
Affiliation IST Austria
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.
Journal Title: Science
Volume: 339
Issue 6115
ISSN: 0036-8075
Publisher: American Association for the Advancement of Science  
Date Published: 2013-01-04
Start Page: 91
End Page: 95
DOI: 10.1126/science.1229858
Open access: no