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Antimicrobial Agents and Chemotherapy, November 2006, p. 3833-3838, Vol. 50, No. 11
0066-4804/06/$08.00+0     doi:10.1128/AAC.00509-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Enhancement of Antimicrobial Activity against Pseudomonas aeruginosa by Coadministration of G10KHc and Tobramycin

Randal Eckert,¹ Keith M. Brady,³ E. Peter Greenberg,^3, Fengxia Qi,² Daniel K. Yarbrough,² Jian He,² Ian McHardy,¹ Maxwell H. Anderson,⁴ and Wenyuan Shi^1,2*

Department of Microbiology, Immunology, and Molecular Genetics,¹ School of Dentistry, University of California, Los Angeles, California 90095,² Department of Microbiology, Roy and Lucille Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242,³ C3 Jian Inc., Sequim, Washington 98382⁴

Received 24 April 2006/ Returned for modification 6 July 2006/ Accepted 14 August 2006

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.

Published ahead of print on 28 August 2006.

Present address: Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195.

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