Zhong, G, Cheng, J, Liang, ZC et al. (7 more authors) (2017) Short Synthetic β-Sheet Antimicrobial Peptides for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Burn Wound Infections. Advanced Healthcare Materials, 6 (7). 1601134. ISSN 2192-2640
Abstract
Pseudomonas aeruginosa is often implicated in burn wound infections; its inherent drug resistance often renders these infections extremely challenging to treat. This is further compounded by the problem of emerging drug resistance and the dearth of novel antimicrobial drug discovery in recent years. In the perennial search for effective antimicrobial compounds, the authors identify short synthetic β-sheet folding peptides, IRIKIRIK (IK8L), IRIkIrIK (IK8-2D), and irikirik (IK8D) as prime candidates owing to their high potency against Gram-negative bacteria. In this study, the peptides are first assayed against 20 clinically isolated multidrug-resistant P. aeruginosa strains in comparison with the conventional antibiotics imipenem and ceftazidime, and IK8L is demonstrated to be the most effective. IK8L also exhibits superior antibacterial killing kinetics compared to imipenem and ceftazidime. From transmission electron microscopy, confocal microscopy, and protein release analyses, IK8L shows membrane-lytic antimicrobial mechanism. Repeated use of IK8L does not induce drug resistance, while the bacteria develop resistance against the antibiotics after several times of treatment at sublethal doses. Analysis of mouse blood serum chemistry reveals that peptide does not induce systemic toxicity. The potential utility of IK8L in the in vivo treatment of P. aeruginosa-infected burn wounds is further demonstrated in a mouse model.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This is the peer reviewed version of the following article: G. Zhong, J. Cheng, Z. C. Liang, L. Xu, W. Lou, C. Bao, Z. Y. Ong, H. Dong, Y. Y. Yang, W. Fan, Adv. Healthcare Mater. 2017, 1601134., which has been published in final form at https://doi.org/10.1002/adhm.201601134. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. |
Keywords: | antimicrobial; burn wounds; infections; multidrug resistance; peptides |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Physics and Astronomy (Leeds) > Molecular & Nanoscale Physics |
Depositing User: | Symplectic Publications |
Date Deposited: | 07 Feb 2017 12:54 |
Last Modified: | 30 Jan 2018 01:38 |
Published Version: | https://doi.org/10.1002/adhm.201601134 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/adhm.201601134 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:111931 |