Issue 9, 2021

A niclosamide–tobramycin hybrid adjuvant potentiates cefiderocol against P. aeruginosa

Abstract

There is an urgent need for new therapies to overcome antimicrobial resistance (AMR) especially against Gram-negative bacilli (GNB). Multicomponent therapy combining antibiotics with enhancer molecules known as adjuvants is an emerging strategy to combat AMR. We have previously reported tobramycin-based adjuvants which are able to potentiate various antibiotics. In order to expand the repertoire of tobramycin hybrid adjuvants, a new hybrid containing niclosamide, an FDA approved anthelmintic which has recently demonstrated a variety of interesting biological effects, was synthesized. It was found that this conjugate can potentiate several antibiotics against multidrug-resistant GNB, including the recently approved siderophore cephalosporin cefiderocol. 8 μg ml−1 of the niclosamide–tobramycin hybrid in combination therapy against a pandrug-resistant strain of P. aeruginosa was able to lower the cefiderocol MIC 32-fold, from 8 μg ml−1 to 0.25 μg ml−1 in iron-rich media where siderophore uptake is reduced. These results indicate that a niclosamide–tobramycin hybrid adjuvant can serve to potentiate a newly approved antibiotic.

Graphical abstract: A niclosamide–tobramycin hybrid adjuvant potentiates cefiderocol against P. aeruginosa

Supplementary files

Article information

Article type
Research Article
Submitted
18 iyn 2021
Accepted
26 iyl 2021
First published
27 iyl 2021

RSC Med. Chem., 2021,12, 1565-1573

A niclosamide–tobramycin hybrid adjuvant potentiates cefiderocol against P. aeruginosa

L. Berry, M. Brizuela, G. Jackson and F. Schweizer, RSC Med. Chem., 2021, 12, 1565 DOI: 10.1039/D1MD00206F

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