Antibacterial activity of nonantibiotics is orthogonal to standard antibiotics.
Science
; 384(6691): 93-100, 2024 Apr 05.
Article
em En
| MEDLINE
| ID: mdl-38484036
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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Microbiota
/
Antibacterianos
Limite:
Humans
Idioma:
En
Revista:
Sci. (N.Y., N.Y.)
/
Science
Ano de publicação:
2024
Tipo de documento:
Article