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Anionic self-assembling supramolecular enhancers of antimicrobial efficacy against Gram-negative bacteria

Boles, Jessica E., Williams, George T., Allen, Nyasha, White, Lisa J., Hilton, Kira L.F., Popoola, Precious, Mulvihill, Daniel P., Hiscock, Jennifer R. (2022) Anionic self-assembling supramolecular enhancers of antimicrobial efficacy against Gram-negative bacteria. Advanced Therapeutics, 5 (5). Article Number 2200024. E-ISSN 2366-3987. (doi:10.1002/adtp.202200024) (KAR id:93507)

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Abstract

As a result of the looming antimicrobial resistance crisis, there is an urgent need for novel antimicrobial treatments. This is particularly true for hard-to-treat Gram-negative bacteria, as many antimicrobial agents are unable to cross the cell membrane to gain access to the cell interior, and thus elicit a therapeutic response. Herein, evidence is provided of the use of anionic supramolecular self-associating amphiphiles (SSAs) as antimicrobial efficacy enhancers for commonly used antimicrobial agents, to which there is known resistance, against Gram-negative bacteria. The co-administration of the SSAs with antimicrobials was shown to sensitise traditionally hard to treat Pseudomonas aeruginosa to both rifampicin and novobiocin, from which structure activity relationships could be elucidated. Quantitative fluorescence microscopy was performed, indicating membrane permeabilization to be the likely mode of action of drug efficacy enhancement by the SSAs. These results offer an alternative strategy in antimicrobial adjuvant design, expanding focus beyond cationic peptides and into the realm of anionic small molecules. Finally, the self-assembly of the SSAs in the presence of these antimicrobials was investigated through a combination of quantitative NMR, tensiometry, dynamic light scattering and zeta potential studies, demonstrating the impact of these agents on SSA self-association events.

Item Type: Article
DOI/Identification number: 10.1002/adtp.202200024
Uncontrolled keywords: supramolecular chemistry, self-assembly, antimicrobial resistance, antimicrobial chemotherapy, membrane binding, fluorescence microscopy
Subjects: Q Science
Q Science > QD Chemistry
Q Science > QD Chemistry > QD431 Organic Chemistry- Biochemistry- Proteins, peptides, amino acids
Divisions: Divisions > Division of Natural Sciences > Chemistry and Forensics
Depositing User: Jennifer Hiscock
Date Deposited: 08 Mar 2022 14:27 UTC
Last Modified: 04 Jul 2023 13:24 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/93507 (The current URI for this page, for reference purposes)

University of Kent Author Information

Mulvihill, Daniel P..

Creator's ORCID: https://orcid.org/0000-0003-2502-5274
CReDIT Contributor Roles:

Hiscock, Jennifer R..

Creator's ORCID: https://orcid.org/0000-0002-1406-8802
CReDIT Contributor Roles:
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