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Development of mechanism-based antibacterial synergy between Fmoc-phenylalanine hydrogel and aztreonam

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Abstract

Recently, fluorenylmethyloxycarbonyl (Fmoc) conjugated amino acids (Fmoc-AA), especially Fmoc-phenylalanine (Fmoc-F), have been discovered to have antimicrobial properties specific to Gram-positive bacteria including MRSA. Their weak antibacterial activity against Gram-negative bacteria is due to their inability to cross the bacterial membrane. Here in order to increase the antibacterial spectrum of Fmoc-F, we prepared a formulation of Fmoc-F with the Gram-negative specific antibiotic aztreonam (AZT). This formulation displayed antibacterial activity against both Gram-positive and Gram-negative bacteria and significantly reduced the bacterial load in a mouse wound infection model. The combination produced a synergistic effect and higher efficacy against P. aeruginosa due to the increased Fmoc-F permeability by AZT through the bacterial membrane. This combinatorial approach could be an effective strategy for other Fmoc-AA having a Gram-positive specific antibacterial effect for the better management of bacterial wound infections.

Graphical abstract: Development of mechanism-based antibacterial synergy between Fmoc-phenylalanine hydrogel and aztreonam

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Article information


Submitted
10 Dec 2019
Accepted
23 Jan 2020
First published
28 Jan 2020

Biomater. Sci., 2020, Advance Article
Article type
Paper

Development of mechanism-based antibacterial synergy between Fmoc-phenylalanine hydrogel and aztreonam

A. Y. Gahane, V. Singh, A. Kumar and A. Kumar Thakur, Biomater. Sci., 2020, Advance Article , DOI: 10.1039/C9BM01978B

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