title: Enhancement of antimicrobial activity against pseudomonas aeruginosa by coadministration of G10KHc and tobramycin.
abstract: Pseudomonas aeruginosa is a common opportunistic human pathogen that is associated with life-threatening acute infections and chronic airway colonization during cystic fibrosis. Previously, we converted the wide-spectrum antimicrobial peptide novispirin G10 into a selectively-targeted antimicrobial peptide (STAMP), G10KHc. Compared to novispirin G10, the STAMP had an enhanced ability to kill Pseudomonas mendocina. In this study, we explored the activity of G10KHc against P. aeruginosa. G10KHc was found to be highly active (as active as tobramycin) against P. aeruginosa clinical isolates. Most interestingly, we observed a synergistic-like enhancement in killing activity when biofilms and planktonic cultures of P. aeruginosa were cotreated with G10KHc and tobramycin. The data indicate that the mechanism of enhanced activity may involve increased tobramycin uptake due to G10KHc-mediated cell membrane disruption. These results suggest that G10KHc may be useful against P. aeruginosa during acute and chronic infection states, especially when it is coadministered with tobramycin.
authors.affiliation: UCLA School of Dentistry, 10833 Le Conte Avenue, Los Angeles, CA 90095-1668, USA.
authors.forename: Randal
authors.initials: R
authors.lastname: Eckert
authors.forename: Keith M
authors.initials: KM
authors.lastname: Brady
authors.forename: E Peter
authors.initials: EP
authors.lastname: Greenberg
authors.forename: Fengxia
authors.initials: F
authors.lastname: Qi
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Yarbrough
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.forename: Ian
authors.initials: I
authors.lastname: McHardy
authors.forename: Maxwell H
authors.initials: MH
authors.lastname: Anderson
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Shi
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D002463:Cell Membrane Permeability / Q000187:drug effects; D004357:Drug Synergism; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D014031:Tobramycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C466663:novispirin G10; D014031:Tobramycin