title: Control of bacterial persister cells by Trp/Arg-containing antimicrobial peptides.
abstract: Persister cells are dormant phenotypic variants inherent in a bacterial population. They play important roles in chronic infections and present great challenges to therapy due to extremely enhanced tolerance to antibiotics compared to that of normal cells of the same genotype. In this study, we report that cationic membrane-penetrating peptides containing various numbers of arginine and tryptophan repeats are effective in killing persister cells of Escherichia coli HM22, a hyper-persister producer. The activities of three linear peptides [(RW)(n)-NH(2), where n is 2, 3, or 4] and a dendrimeric peptide, (RW)(4D), in killing bacterial persisters were compared. Although the dendrimeric peptide (RW)(4D) requires a lower threshold to kill planktonic persisters, octameric peptide (RW)(4)-NH(2) is the most effective against planktonic persister cells at high concentrations. For example, treatment with 80 μM (RW)(4)-NH(2) for 60 min led to a 99.7% reduction in the number of viable persister cells. The viability of persister cells residing in surface-attached biofilms was also significantly reduced by (RW)(4)-NH(2) and (RW)(4D). These two peptides were also found to significantly enhance the susceptibility of biofilm cells to ofloxacin. The potency of (RW)(4)-NH(2) was further marked by its ability to disperse and kill preformed biofilms harboring high percentages of persister cells. Interestingly, approximately 70% of the dispersed cells were found to have lost their intrinsic tolerance and become susceptible to ampicillin if not killed directly by this peptide. These results are helpful for better understanding the activities of these peptides and may aid in future development of more effective therapies of chronic infections.
authors.affiliation: Department of Biology, Syracuse University, Syracuse, NY 13244, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Mi
authors.initials: M
authors.lastname: Zhang
authors.forename: Chunhui
authors.initials: C
authors.lastname: Zhou
authors.forename: Neville R
authors.initials: NR
authors.lastname: Kallenbach
authors.forename: Dacheng
authors.initials: D
authors.lastname: Ren
mesh_terms: D000667:Ampicillin; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin; D009842:Oligopeptides; D010933:Plankton / Q000187:drug effects / Q000254:growth & development
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D009842:Oligopeptides; C092608:arginyl-tryptophyl-arginine; D000667:Ampicillin; D015242:Ofloxacin