A potent and selective antimicrobial poly(amidoamine) dendrimer conjugate with LED209 targeting QseC receptor to inhibit the virulence genes of gram negative bacteria
Copyright © 2015 Elsevier Inc. All rights reserved..
The pandemic of multidrug-resistant Gram negative bacteria (GNB) is a worldwide healthcare concern, and very few antibiotics are being explored to match the clinical challenge. Recently, amino-terminated poly(amidoamine) (PAMAM) dendrimers have shown potential to function as broad antimicrobial agents. However, PAMAM displays a generation dependent cytotoxicity to mammalian cells and low selectivity on bacterial cells, which limits PAMAM to be developed as an antibacterial agent for systemic administration. We conjugated G3 PAMAM with LED209, a specific inhibitor of quorum sensor QseC of GNB, to generate a multifunctional agent PAMAM-LED209. Intriguingly, PAMAM-LED209 showed higher selectivity on GNB and lower cytotoxicity to mammalian cells, yet remained strong antibacterial activity. PAMAM-LED209 also inhibited virulence gene expression of GNB, and did not induce antibiotic-resistance. The present work firstly demonstrated that PAMAM-LED209 conjugate had a highly selective anti-GNB activity and low cytotoxicity, which offered a feasible strategy for combating multidrug-resistant GNB infections.
FROM THE CLINICAL EDITOR: This research team demonstrated that a novel PAMAM-LED209 conjugate had highly selective activity against Gram-negative bacteria, coupled with low cytotoxicity, offering a potential strategy for combating multidrug-resistant infections.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Nanomedicine : nanotechnology, biology, and medicine - 11(2015), 2 vom: 21. Feb., Seite 329-39 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xue, Xiao-Yan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.11.2015 Date Revised 09.03.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.nano.2014.09.016 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM244153566 |
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| 100 | 1 | |a Xue, Xiao-Yan |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A potent and selective antimicrobial poly(amidoamine) dendrimer conjugate with LED209 targeting QseC receptor to inhibit the virulence genes of gram negative bacteria |
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| 500 | |a Date Revised 09.03.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2015 Elsevier Inc. All rights reserved. | ||
| 520 | |a The pandemic of multidrug-resistant Gram negative bacteria (GNB) is a worldwide healthcare concern, and very few antibiotics are being explored to match the clinical challenge. Recently, amino-terminated poly(amidoamine) (PAMAM) dendrimers have shown potential to function as broad antimicrobial agents. However, PAMAM displays a generation dependent cytotoxicity to mammalian cells and low selectivity on bacterial cells, which limits PAMAM to be developed as an antibacterial agent for systemic administration. We conjugated G3 PAMAM with LED209, a specific inhibitor of quorum sensor QseC of GNB, to generate a multifunctional agent PAMAM-LED209. Intriguingly, PAMAM-LED209 showed higher selectivity on GNB and lower cytotoxicity to mammalian cells, yet remained strong antibacterial activity. PAMAM-LED209 also inhibited virulence gene expression of GNB, and did not induce antibiotic-resistance. The present work firstly demonstrated that PAMAM-LED209 conjugate had a highly selective anti-GNB activity and low cytotoxicity, which offered a feasible strategy for combating multidrug-resistant GNB infections | ||
| 520 | |a FROM THE CLINICAL EDITOR: This research team demonstrated that a novel PAMAM-LED209 conjugate had highly selective activity against Gram-negative bacteria, coupled with low cytotoxicity, offering a potential strategy for combating multidrug-resistant infections | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Antimicrobial resistance | |
| 650 | 4 | |a Gram negative bacteria | |
| 650 | 4 | |a LED209 | |
| 650 | 4 | |a Poly(amidoamine) dendrimer | |
| 650 | 4 | |a QseC | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a Bacterial Proteins |2 NLM | |
| 650 | 7 | |a Dendrimers |2 NLM | |
| 650 | 7 | |a LED209 |2 NLM | |
| 650 | 7 | |a PAMAM Starburst |2 NLM | |
| 650 | 7 | |a QscR protein, Pseudomonas aeruginosa |2 NLM | |
| 650 | 7 | |a Repressor Proteins |2 NLM | |
| 650 | 7 | |a Sulfonamides |2 NLM | |
| 700 | 1 | |a Mao, Xing-Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zhi |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Zhou |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Zheng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ming-Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Meng, Jing-Ru |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Xiao-Xing |e verfasserin |4 aut | |
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