I have a long standing interest in persister cells and their contribution to bacterial survival. Persisters are phenotypic variants of wild type cells, which survive antibiotic treatment.

Tuberculosis continues to be a major public health problem in many parts of the world. Significant obstacles in controlling the epidemic are the length of treatment and the large reservoir of latently infected people.We hypothesize that persister cells contribute to the need of lengthy treatment and latency.

We are employing several approaches to characterize M. tuberculosis persisters. These include isolating high persister (hip) mutants, transcriptome analysis, whole genome sequencing, cell sorting and more.

Publications:

Keren I, Wu Y, Julio Inocencio, Lawrence R. Mulcahy, Lewis K. (2013) Killing by Bactericidal Antibiotics Does Not Depend on Reactive Oxygen Species. Science. 339(6124): 1213-1216.

Constance J. Martin, Matthew G. Booty, Tracy R. Rosebrock, Cláudio Nunes-Alves, Danielle M. Desjardins, Iris Keren, Sarah M. Fortune, Heinz G. Remold, Samuel M. Behar. (2012) Efferocytosis Is an Innate Antibacterial Mechanism.Cell Host & Microbe.12(3): 289-300 [PDF]

Wu Y, Vulic M, Keren I, Lewis K. (2012) Role of oxidative stress in persister tolerance. AAC. 56(9):4922-6. [PDF]

Keren I, Minami S, Rubin E, Lewis K. (2011) Characterization and transcriptome analysis of Mycobacterium tuberculosis persisters. mBio. 2:3 e00100-11. [PDF]

Lewis K, Spoering A, Kaldalu N, Keren I, and Shah D. (2005) Persisters: specialized cells responsible for biofilm tolerance to antimicrobial agents. Biofilms, Infection, and Antimicrobial Therapy. Pace, J., Rupp, M.E. and Finch, R.G. (eds). Boca Raton, London, New York, Singapore: Taylor & Francis, pp. 241-256.

Keren I, Shah D, Spoering A, Kaldalu N, and Lewis K. (2004) Specialized persister cells and the mechanism of multidrug tolerance in Escherichia coli. J Bacteriol. 186:8172-80. [PDF]

Keren I, Kaldalu N, Spoering A, Wang Y, and Lewis K. (2004) Persister cells and tolerance to antimicrobials. FEMS Microbiol. Lett. 230:13-18. [PDF]

Karen A, Duca1, Vy Lam, Iris Keren, Elizabeth E Endler, Geoffrey J Letchworth, Isabel S Novella, John Yin. (2001) Quantifying viral propagation in vitro: toward a method for characterization of complex phenotypes. Biotechnology Progress. 17(6):1156-1165. [PDF]

Keren, I. and Moshe Sheintuch (2000). Modeling and analysis of spatiotemporal oscillatory patterns during CO oxidation in the catalytic converter. Chemical Engineering Science. 55(8):1461-1475. [PDF]