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Antibacterial activity of nonantibiotics is orthogonal to standard antibiotics.

Authors :
Noto Guillen M
Li C
Rosener B
Mitchell A
Source :
Science (New York, N.Y.) [Science] 2024 Apr 05; Vol. 384 (6691), pp. 93-100. Date of Electronic Publication: 2024 Mar 14.
Publication Year :
2024

Abstract

Numerous nonantibiotic drugs have potent antibacterial activity and can adversely affect the human microbiome. The mechanistic underpinning of this toxicity remains largely unknown. We investigated the antibacterial activity of 200 drugs using genetic screens with thousands of barcoded Escherichia coli knockouts. We analyzed 2 million gene-drug interactions underlying drug-specific toxicity. Network-based analysis of drug-drug similarities revealed that antibiotics clustered into modules that are consistent with the mode of action of their established classes, whereas nonantibiotics remained unconnected. Half of the nonantibiotics clustered into separate modules, potentially revealing shared and unexploited targets for new antimicrobials. Analysis of efflux systems revealed that they widely affect antibiotics and nonantibiotics alike, suggesting that the impact of nonantibiotics on antibiotic cross-resistance should be investigated closely in vivo.

Details

Language :
English
ISSN :
1095-9203
Volume :
384
Issue :
6691
Database :
MEDLINE
Journal :
Science (New York, N.Y.)
Publication Type :
Academic Journal
Accession number :
38484036
Full Text :
https://doi.org/10.1126/science.adk7368