Wakamoto, Yurichi ; Dhar, Neraaj ; Chait, Remy PIST Austria ; Schneider, Katrin ; Signorino Gelo, François ; Leibler, Stanislas ; Mckinney, John
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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Wakamoto Y, Dhar N, Chait RP, et al. Dynamic persistence of antibiotic-stressed mycobacteria. Science. 2013;339(6115):91-95. doi:10.1126/science.1229858
Wakamoto, Y., Dhar, N., Chait, R. P., Schneider, K., Signorino Gelo, F., Leibler, S., & Mckinney, J. (2013). Dynamic persistence of antibiotic-stressed mycobacteria. Science, 339(6115), 91–95. https://doi.org/10.1126/science.1229858
Wakamoto, Yurichi, Neraaj Dhar, Remy P Chait, Katrin Schneider, François Signorino Gelo, Stanislas Leibler, and John Mckinney. “Dynamic Persistence of Antibiotic-Stressed Mycobacteria.” Science 339, no. 6115 (2013): 91–95. https://doi.org/10.1126/science.1229858.
Y. Wakamoto et al., “Dynamic persistence of antibiotic-stressed mycobacteria,” Science, vol. 339, no. 6115, pp. 91–95, 2013.
Wakamoto Y, Dhar N, Chait RP, Schneider K, Signorino Gelo F, Leibler S, Mckinney J. 2013. Dynamic persistence of antibiotic-stressed mycobacteria. Science. 339(6115), 91–95.
Wakamoto, Yurichi, et al. “Dynamic Persistence of Antibiotic-Stressed Mycobacteria.” Science, vol. 339, no. 6115, American Association for the Advancement of Science, 2013, pp. 91–95, doi:10.1126/science.1229858.