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A Common Platform for Antibiotic Dereplication and Adjuvant Discovery

Cox, Georgina and Sieron, Arthur and King, Andrew and De Pascale, Gianfranco and Pawlowski, Andrew and Koteva, Kalinka and Wright, Gerard (2017) A Common Platform for Antibiotic Dereplication and Adjuvant Discovery. Cell chemical biology, 24. pp. 98-109. ISSN 2451-9456

Abstract

Solving the antibiotic resistance crisis requires the discovery of new antimicrobial drugs
and the preservation of existing ones. A major difficulty in identifying new antibiotics, in
particular from microbes, is the frequent re-discovery of known compounds. This
necessitates the laborious ‘dereplication’ of known compounds to identify novel
molecules. We have developed an antibiotic resistance platform (ARP) that can be used
for both antibiotic dereplication and for the identification of inhibitors of resistance that
rescue existing drugs, antibiotic adjuvants. The ARP is a cell-based array of well characterized
individual resistance elements in an identical genetic background. In
dereplication mode, we demonstrate the facile identification of known antibiotics by a
simple plate-based overlay approach allowing rapid discrimination of common
antibiotics. In resistance inhibition mode, we show that the ARP can be harnessed in
screens for antibiotic adjuvant compounds. The ARP is therefore a powerful tool with
broad application in overcoming the resistance crisis.

Item Type: Article
Date Deposited: 25 Jan 2017 00:45
Last Modified: 25 Jan 2017 00:45
URI: https://oak.novartis.com/id/eprint/29232

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