Enhancement of antimicrobial activity against Pseudomonas aeruginosa by coadministration of G10KHc and tobramycin

Randal Eckert, Keith M. Brady, E. Peter Greenberg, Fengxia Qi, Daniel K. Yarbrough, Jian He, Ian Howard Mchardy, Maxwell H. Anderson, Wenyuan Shi

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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.

Original languageEnglish (US)
Pages (from-to)3833-3838
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume50
Issue number11
DOIs
StatePublished - Nov 2006

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ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Eckert, R., Brady, K. M., Greenberg, E. P., Qi, F., Yarbrough, D. K., He, J., Mchardy, I. H., Anderson, M. H., & Shi, W. (2006). Enhancement of antimicrobial activity against Pseudomonas aeruginosa by coadministration of G10KHc and tobramycin. Antimicrobial Agents and Chemotherapy, 50(11), 3833-3838. https://doi.org/10.1128/AAC.00509-06