Mehmet Orman: Bacterial Persistence: A Metabolically-Stimulated State
Location:131 DeBartolo Hall
Bacterial persisters are rare, phenotypic variants that are temporarily tolerant to high concentrations of antibiotics. Persisters have been hypothesized to underlie the recalcitrance of biofilm infections, and strategies to eliminate these cells have the potential to improve treatment outcomes for the majority of hospital-treated infections. The low abundance, transient nature, and similarities of persisters to other cell-types have hindered progress toward understanding their physiology. In particular, knowledge of persister metabolism remains scarce. We investigated the role of metabolism in persisters arising from stationary phase cultures, which is the stage of growth where persisters are most abundant. Within this nutrient-depleted environment, we discovered that persisters are far less likely to derive from bacteria with low metabolic activity, and found that inhibition of metabolism, but not macromolecular synthesis, during stationary phase reduced persistence drastically. We determined that loss of stationary phase metabolic activity prevented digestion of endogenous proteins and RNA, which yielded bacteria that were more capable of translation, replication, and concomitantly cell death when exposed to antibiotics. Overall, these observations highlight a central role for metabolism in persister formation, and demonstrate its potential to provide anti-persister strategies.
Memorial Sloan Kettering Cancer Center
Mehmet obtained his B.S. and M.S. degrees from the Chemical Engineering Department at Middle East Technical University in Ankara, Turkey in 2007, and his Ph.D. in Chemical and Biochemical Engineering from Rutgers University in 2011. Previously, he was a postdoctoral research associate at the Chemical and Biological Engineering Department at Princeton University, until 2015. He then joined the Memorial Sloan Kettering Cancer Center, the world’s leading cancer research center, as a research fellow to gain more insights within the cancer research field. In his research, he utilizes systems biology, metabolic engineering, and molecular genetic tools to understand biological problems that impose a huge burden on the health care system. His diverse research interests include: understanding inflammation induced-hypermetabolic state; characterizing the physiology of reversible drug tolerant phenotypes; and studying DNA repair mechanisms in cancer cells. His pivotal research proposal in persistence has recently received the best possible impact score of 10 from the NIH for the K22 Career Transition Award, which supports tenure-track assistant professors within the first two years of their academic career.