Antimicrobial Polypeptides Capable of Membrane Translocation for Treatment of MRSA Wound Infection In Vivo

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Antimicrobial Polypeptides Capable of Membrane Translocation for Treatment of MRSA Wound Infection In Vivo
Title:
Antimicrobial Polypeptides Capable of Membrane Translocation for Treatment of MRSA Wound Infection In Vivo
Other Titles:
Advanced Healthcare Materials
Publication Date:
30 November 2021
Citation:
Yang, S., Wang, Y., Tan, J., Teo, J. Y., Tan, K. H., & Yang, Y. Y. (2021). Antimicrobial Polypeptides Capable of Membrane Translocation for Treatment of MRSA Wound Infection In Vivo. Advanced Healthcare Materials, 11(6), 2101770. Portico. https://doi.org/10.1002/adhm.202101770
Abstract:
Multidrug resistant infections are plaguing the healthcare sector over the past few decades with limited treatment options. To overcome this problem, the authors synthesize a series of novel guanidinium-functionalized polypeptides. Specifically, poly(l-lysine) (PLL) with different lengths is first synthesized by ring-opening polymerization of Nε-benzyloxycarbonyl-l-lysine-N-carboxyanhydride (Lys(Z)-NCA) followed by functionalization with a guanidinium-functional group to obtain guanidinium-functionalized PLL (PLL-Gua). To study the effect of hydrophobicity on antimicrobial activity, relatively more hydrophobic leucine-NCA monomer or hydrophobic vitamin E moiety is introduced to PLL-Gua. These polypeptides are characterized for antimicrobial activity against a panel of microbes including multidrug-resistant bacteria, and hemolytic activity. Among all the polypeptides, PLL22-Gua is most effective against bacteria and yeast. Particularly, excellent bactericidal activity is observed against Staphylococcus aureus and MRSA. PLL22-Gua kills bacteria mainly by membrane translocation. In addition, PLL22-Gua kills MRSA with low resistance frequency (<3.3 × 10−8). In an MRSA-caused wound infection mouse model, two-day treatment (twice daily) with 10, 20, or 40 mg per kg of PLL22-Gua shows up to 99.5% bacterial removal. Moreover, no acute dermal toxicity is observed even at a dose of 200 mg per kg. These promising results show the excellent potential of PLL22-Gua as an antimicrobial agent against multidrug-resistant infection in vivo.
License type:
Publisher Copyright
Funding Info:
This research is supported by core funding from: Institute of Bioengineering and Bioimaging
Grant Reference no. : SC19-R0002
Description:
This is the peer reviewed version of the following article: Yang, S., Wang, Y., Tan, J., Teo, J. Y., Tan, K. H., & Yang, Y. Y. (2021). Antimicrobial Polypeptides Capable of Membrane Translocation for Treatment of MRSA Wound Infection In Vivo. Advanced Healthcare Materials, 11(6), 2101770. Portico. https://doi.org/10.1002/adhm.202101770, which has been published in final form at doi.org/10.1002/adhm.202101770. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
ISSN:
2192-2659
2192-2640
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