Antimicrobial nanoplexes meet model bacterial membranes: the key role of Cardiolipin

Marín-Menéndez, Alejandro, Montis, Costanza, Díaz-Calvo, Teresa, Carta, Davide, Hatzixanthis, Kostas, Morris, Christopher J. ORCID:, McArthur, Michael and Berti, Debora (2017) Antimicrobial nanoplexes meet model bacterial membranes: the key role of Cardiolipin. Scientific Reports, 7. ISSN 2045-2322

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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.

Item Type: Article
Faculty \ School: Faculty of Science > School of Pharmacy
Faculty of Science > School of Biological Sciences
Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Science > Research Groups > Pharmaceutical Materials and Soft Matter
Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User: Pure Connector
Date Deposited: 18 Jan 2017 00:03
Last Modified: 31 Jan 2024 02:14
DOI: 10.1038/srep41242


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