Marín-Menéndez, Alejandro;
Montis, Costanza;
Díaz-Calvo, Teresa;
Carta, Davide;
Hatzixanthis, Kostas;
Morris, Christopher J;
McArthur, Michael;
(2017)
Antimicrobial Nanoplexes meet Model Bacterial Membranes: the key role of Cardiolipin.
Scientific Reports
, 7
, Article 41242. 10.1038/srep41242.
Preview |
PDF
Antimicrobial Nanoplexes meet Model Bacterial Membranes the key role of Cardiolipin.pdf - Published Version Download (2MB) | Preview |
Abstract
Antimicrobial resistance to traditional antibiotics is a crucial challenge of medical research. Oligonucleotide therapeutics, such as antisense or Transcription Factor Decoys (TFDs), have the potential to circumvent current resistance mechanisms by acting on novel targets. However, their full translation into clinical application requires efficient delivery strategies and fundamental comprehension of their interaction with target bacterial cells. To address these points, we employed a novel cationic bolaamphiphile that binds TFDs with high affinity to form self-Assembled complexes (nanoplexes). Confocal microscopy revealed that nanoplexes efficiently transfect bacterial cells, consistently with biological efficacy on animal models. To understand the factors affecting the delivery process, liposomes with varying compositions, taken as model synthetic bilayers, were challenged with nanoplexes and investigated with Scattering and Fluorescence techniques. Thanks to the combination of results on bacteria and synthetic membrane models we demonstrate for the first time that the prokaryotic-enriched anionic lipid Cardiolipin (CL) plays a key-role in the TFDs delivery to bacteria. Moreover, we can hypothesize an overall TFD delivery mechanism, where bacterial membrane reorganization with permeability increase and release of the TFD from the nanoplexes are the main factors. These results will be of great benefit to boost the development of oligonucleotides-based antimicrobials of superior efficacy.
| Type: | Article |
|---|---|
| Title: | Antimicrobial Nanoplexes meet Model Bacterial Membranes: the key role of Cardiolipin |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/srep41242 |
| Publisher version: | https://doi.org/10.1038/srep41242 |
| Language: | English |
| Additional information: | © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Drug delivery |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10159839 |
Loading...
Loading...Loading...| 1. |  China | 2 |
| 2. |  Egypt | 1 |
Archive Staff Only
 |
View Item |
