Persister cells are commonly found as a small fraction of dormant cells in a bacterial population that are extremely tolerant to antibiotics. Such intrinsic tolerance plays important roles in chronic infection and presents a great challenge to therapy. Here we report that cationic membrane-penetrating peptides are effective in killing persister cells of Escherichia coli.
Four antimicrobial peptides (AMPs) with various numbers of arginine and tryptophan repeats were rigorously compared including three linear peptides [(RW)n-NH2, where n=2,3, or 4] and a dendrimeric peptide [(RW)4D]. E. coli HM22, a hyper persister producer, was used in this study to obtain high titers of persister cells. Among the AMPs tested, the octameric peptide is the most effective AMP against planktonic persister cells. For example, treatment with 80 ÁM of this peptide for 60 min reduced the number of viable persister cells by more than three logs. Octameric and dendrimeric peptides were also found to be effective against persister cells in biofilms (surface-attached sessile colonies). An up to 99% reduction in viability was observed for biofilm persisters treated with octameric [(RW)4] or dendrimeric [(RW)4D] peptide. The potency of octameric peptide was further marked by its ability to detach the preformed biofilms harboring persister cells. Interestingly, once detached, approximately 70% of the persister population appeared to be susceptible to ampicillin if not killed immediately by this peptide. These results are helpful for better understanding the mechanism of persister formation and development of more effective therapies.