Pu, YingyingZhao, ZhilunLi, YingxingZou, JinMa, QiZhao, YannaKe, YuehuaZhu, YunChen, HuiyiBaker, Matthew A.B.Ge, HaoSun, YujieXie, Xiaoliang SunneyBai, Fan2016-06-142016Pu, Y., Z. Zhao, Y. Li, J. Zou, Q. Ma, Y. Zhao, Y. Ke, et al. 2016. “Enhanced Efflux Activity Facilitates Drug Tolerance in Dormant Bacterial Cells.” Molecular Cell 62 (2): 284-294. doi:10.1016/j.molcel.2016.03.035. http://dx.doi.org/10.1016/j.molcel.2016.03.035.1097-2765http://nrs.harvard.edu/urn-3:HUL.InstRepos:27320424Summary Natural variations in gene expression provide a mechanism for multiple phenotypes to arise in an isogenic bacterial population. In particular, a sub-group termed persisters show high tolerance to antibiotics. Previously, their formation has been attributed to cell dormancy. Here we demonstrate that bacterial persisters, under β-lactam antibiotic treatment, show less cytoplasmic drug accumulation as a result of enhanced efflux activity. Consistently, a number of multi-drug efflux genes, particularly the central component TolC, show higher expression in persisters. Time-lapse imaging and mutagenesis studies further establish a positive correlation between tolC expression and bacterial persistence. The key role of efflux systems, among multiple biological pathways involved in persister formation, indicates that persisters implement a positive defense against antibiotics prior to a passive defense via dormancy. Finally, efflux inhibitors and antibiotics together effectively attenuate persister formation, suggesting a combination strategy to target drug tolerance.en-USJournal Article2016-06-1410.1016/j.molcel.2016.03.035