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Persister Cells

Persisters are bacterial cells able to survive killing by antibiotics. This antibiotic tolerance is mechanistically distinct from resistance. Persisters are not mutants but phenotypic variants.

We are interested in genetic mechanism(s) underlying formation of persister fraction within genetically identical antibiotic-susceptible population of bacteria. Understanding these mechanisms is important in order to get a complete and realistic picture of pathogens during the infection and antibiotic treatement, especially in the case of chronic and relapsing infections. In addition there is an interest in uncovering the mechanism of generation of phenotypic diversity and its role and significance in evolution.

Current projects involve isolation and characterization of high persistence mutants in Escherichia coli and Yersinia pestis, characterization of E. coli knock-out mutants exhibiting low persistence phenotype, the link between stress responses (SOS and heat shock) and persistence and the role of recombination and SOS-functions in persistance to fluoroquinolones.

Members:

Persister Cells Selected Publications:

Schumacher, M.A., Piro, K.M., Xu, W., Hansen, S., Lewis, K., and Brennan, R.G. (2009). Molecular Mechanisms of HipA Mediated Multidrug Tolerance and its Neutralization by HipB. Accepted in Science.

Lewis K. (2008).Multidrug tolerance of biofilms and persister cells. Curr Top Microbiol Immunol. 322:107-31. Review.

Lewis, K. (2007) Persister cells, dormancy and infectious disease. Nat. Rev. Microbiol. 5:48-56. [PDF]

Correia, FF., D’Onofrio, A., Rejtar, T., Li, L., Karger, BL., Makarova, K., Koonin, EV., and Lewis, K. (2006) Kinase activity of overexpressed HipA is required for growth arrest and multidrug tolerance in Escherichia coli. J. Bacteriol. 188:8360-7. [PDF]

Shah D, Zhang Z, Khodursky AB, Kaldalu N, Kurg K, Lewis K. (2006) Persisters: a distinct physiological state of E. coli. BMC Microbiology. 6:53

LaFleur, MD., Kumamoto, CA., and Lewis, K. (2006) Candida albicans biofilms produce antifungal-tolerant persister cells. Antimicrob. Agents Chemother. 50:3839-46. [PDF]

Spoering, A.L., Vulic, M., Lewis, K. (2006) GlpD and PlsB Participate in Persister Cell Formation in Escherichia coli. J. Bacteriol. 188:5136-44. [PDF]

Lewis K. (2005). Persister cells and the riddle of biofilm survival. Biochemistry. (Mosc);70(2):267-74.

Lewis, K., Spoering, A., Kaldalu, N., Keren, I., and Shah, D. (2005) Persisters: Specialized Cells Responsible For Biofilm Tolerance To Antimicrobial Agents. In 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]

Kaldalu, N., Mei, R., and Lewis, K. (2004) Killing by ampicillin and ofloxacin induces overlapping changes in Escherichia coli transcription profile. Antimicrob. Agents Chemother. 48:890-896.

Spoering, A.L. and Lewis, K. (2001) Biofilms and Planktonic Cells of Pseudomonas aeruginosa Have Similar Resistance to Killing by Antimicrobials. J. Bacteriol. 183:6746-6751. [PDF]

Lewis K. (2001). Riddle of biofilm resistance. Antimicrob Agents Chemother. 45(4):999-1007.

Brooun, A., Liu, S., and Lewis, K. (2000) A Dose-Response Study of Antibiotic Resistance in Pseudomonas aeruginosa Biofilms. Antimicrob. Agents Chemother. 44:640-646. [PDF]