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Novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus
Infections caused by multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), have become a public threat; therefore, development of new antimicrobial drugs or strategies is urgently required. In this study, a new antibacterial peptide DP7-C (Chol-suc-VQWRIRVAVIRK-NH...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167457/ https://www.ncbi.nlm.nih.gov/pubmed/28008253 http://dx.doi.org/10.2147/IJN.S107107 |
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author | Liu, Xiaowei Li, Zhan Wang, Xiaodong Chen, Yujuan Wu, Fengbo Men, Ke Xu, Ting Luo, Yan Yang, Li |
author_facet | Liu, Xiaowei Li, Zhan Wang, Xiaodong Chen, Yujuan Wu, Fengbo Men, Ke Xu, Ting Luo, Yan Yang, Li |
author_sort | Liu, Xiaowei |
collection | PubMed |
description | Infections caused by multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), have become a public threat; therefore, development of new antimicrobial drugs or strategies is urgently required. In this study, a new antibacterial peptide DP7-C (Chol-suc-VQWRIRVAVIRK-NH2) and DP7-C-modified azithromycin (AZT)-loaded liposomes (LPs) are developed for the treatment of MRSA infection, and it was found that DP7-C inserted into the LP lipid bilayer not only functioned as a carrier to encapsulate the antibiotic AZT but also synergized the antibacterial effect of the encapsulated AZT. In vitro assays showed that DP7-C-modified LPs possessed sustained drug release profile and immune regulatory effect and did not show obvious cytotoxicity in mammal cells, but they did not possess direct antibacterial activity in vitro. In vivo studies revealed that DP7-C-modified LPs did not exhibit obvious side effects or toxicity in mice but were able to significantly reduce the bacterial counts in an MRSA-infectious mouse model and possessed high antibacterial activity. In particular, DP7-C-modified AZT-loaded LPs showed more positive therapeutic effects than either DP7-C-modified blank LPs or nonmodified AZT-loaded LPs treatment alone. Molecular mechanism studies demonstrated that DP7-C formulations effectively upregulated the production of anti-inflammatory cytokines and chemokines without inducing harmful immune response, suggesting that DP7-C was synergistic with AZT against the bacterial infection by activating the innate immune response. Most importantly, although DP7-C activated the innate immune response, it did not possess direct antibacterial activity in vitro, indicating that DP7-C did not possess the potential to induce bacteria resistance. The findings indicate that DP7-C-modified AZT-loaded LPs developed in this study have a great potential required for the clinical treatment of MRSA infections. |
format | Online Article Text |
id | pubmed-5167457 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-51674572016-12-22 Novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus Liu, Xiaowei Li, Zhan Wang, Xiaodong Chen, Yujuan Wu, Fengbo Men, Ke Xu, Ting Luo, Yan Yang, Li Int J Nanomedicine Original Research Infections caused by multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), have become a public threat; therefore, development of new antimicrobial drugs or strategies is urgently required. In this study, a new antibacterial peptide DP7-C (Chol-suc-VQWRIRVAVIRK-NH2) and DP7-C-modified azithromycin (AZT)-loaded liposomes (LPs) are developed for the treatment of MRSA infection, and it was found that DP7-C inserted into the LP lipid bilayer not only functioned as a carrier to encapsulate the antibiotic AZT but also synergized the antibacterial effect of the encapsulated AZT. In vitro assays showed that DP7-C-modified LPs possessed sustained drug release profile and immune regulatory effect and did not show obvious cytotoxicity in mammal cells, but they did not possess direct antibacterial activity in vitro. In vivo studies revealed that DP7-C-modified LPs did not exhibit obvious side effects or toxicity in mice but were able to significantly reduce the bacterial counts in an MRSA-infectious mouse model and possessed high antibacterial activity. In particular, DP7-C-modified AZT-loaded LPs showed more positive therapeutic effects than either DP7-C-modified blank LPs or nonmodified AZT-loaded LPs treatment alone. Molecular mechanism studies demonstrated that DP7-C formulations effectively upregulated the production of anti-inflammatory cytokines and chemokines without inducing harmful immune response, suggesting that DP7-C was synergistic with AZT against the bacterial infection by activating the innate immune response. Most importantly, although DP7-C activated the innate immune response, it did not possess direct antibacterial activity in vitro, indicating that DP7-C did not possess the potential to induce bacteria resistance. The findings indicate that DP7-C-modified AZT-loaded LPs developed in this study have a great potential required for the clinical treatment of MRSA infections. Dove Medical Press 2016-12-14 /pmc/articles/PMC5167457/ /pubmed/28008253 http://dx.doi.org/10.2147/IJN.S107107 Text en © 2016 Liu et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Liu, Xiaowei Li, Zhan Wang, Xiaodong Chen, Yujuan Wu, Fengbo Men, Ke Xu, Ting Luo, Yan Yang, Li Novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus |
title | Novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus |
title_full | Novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus |
title_fullStr | Novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus |
title_full_unstemmed | Novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus |
title_short | Novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant Staphylococcus aureus |
title_sort | novel antimicrobial peptide–modified azithromycin-loaded liposomes against methicillin-resistant staphylococcus aureus |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167457/ https://www.ncbi.nlm.nih.gov/pubmed/28008253 http://dx.doi.org/10.2147/IJN.S107107 |
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