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

Research output: Contribution to journalArticle

47 Citations (Scopus)

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

Fingerprint

Tobramycin
Pseudomonas aeruginosa
Pseudomonas mendocina
Peptides
Biofilms
Infection
Cystic Fibrosis
Cell Membrane

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Enhancement of antimicrobial activity against Pseudomonas aeruginosa by coadministration of G10KHc and tobramycin. / Eckert, Randal; Brady, Keith M.; Greenberg, E. Peter; Qi, Fengxia; Yarbrough, Daniel K.; He, Jian; Mchardy, Ian Howard; Anderson, Maxwell H.; Shi, Wenyuan.

In: Antimicrobial Agents and Chemotherapy, Vol. 50, No. 11, 11.2006, p. 3833-3838.

Research output: Contribution to journalArticle

Eckert, Randal ; Brady, Keith M. ; Greenberg, E. Peter ; Qi, Fengxia ; Yarbrough, Daniel K. ; He, Jian ; Mchardy, Ian Howard ; Anderson, Maxwell H. ; Shi, Wenyuan. / Enhancement of antimicrobial activity against Pseudomonas aeruginosa by coadministration of G10KHc and tobramycin. In: Antimicrobial Agents and Chemotherapy. 2006 ; Vol. 50, No. 11. pp. 3833-3838.
@article{bb8932df168f4012911622f11e9328fd,
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.",
author = "Randal Eckert and Brady, {Keith M.} and Greenberg, {E. Peter} and Fengxia Qi and Yarbrough, {Daniel K.} and Jian He and Mchardy, {Ian Howard} and Anderson, {Maxwell H.} and Wenyuan Shi",
year = "2006",
month = "11",
doi = "10.1128/AAC.00509-06",
language = "English (US)",
volume = "50",
pages = "3833--3838",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "11",

}

TY - JOUR

T1 - Enhancement of antimicrobial activity against Pseudomonas aeruginosa by coadministration of G10KHc and tobramycin

AU - Eckert, Randal

AU - Brady, Keith M.

AU - Greenberg, E. Peter

AU - Qi, Fengxia

AU - Yarbrough, Daniel K.

AU - He, Jian

AU - Mchardy, Ian Howard

AU - Anderson, Maxwell H.

AU - Shi, Wenyuan

PY - 2006/11

Y1 - 2006/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33750577582&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750577582&partnerID=8YFLogxK

U2 - 10.1128/AAC.00509-06

DO - 10.1128/AAC.00509-06

M3 - Article

C2 - 16940063

AN - SCOPUS:33750577582

VL - 50

SP - 3833

EP - 3838

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 11

ER -