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Nat Commun. 2014 Jul 8;5:4352. doi: 10.1038/ncomms5352.

Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network.

Author information

1
1] Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Temesvari krt 62, Szeged 6726, Hungary [2].
2
1] Sequencing Platform, Institute of Biochemistry, Biological Research Centre, Temesvari krt 62, Szeged 6726, Hungary [2].
3
Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Temesvari krt 62, Szeged 6726, Hungary.
4
Sequencing Platform, Institute of Biochemistry, Biological Research Centre, Temesvari krt 62, Szeged 6726, Hungary.
5
MTA-SZTE Research Group on Artificial Intelligence, Tisza Lajos krt 103., H-6720 Szeged, Hungary.
6
Linear Accelerator Laboratory, University of Paris-Sud, CNRS, Orsay 91898, France.

Abstract

Understanding how evolution of antimicrobial resistance increases resistance to other drugs is a challenge of profound importance. By combining experimental evolution and genome sequencing of 63 laboratory-evolved lines, we charted a map of cross-resistance interactions between antibiotics in Escherichia coli, and explored the driving evolutionary principles. Here, we show that (1) convergent molecular evolution is prevalent across antibiotic treatments, (2) resistance conferring mutations simultaneously enhance sensitivity to many other drugs and (3) 27% of the accumulated mutations generate proteins with compromised activities, suggesting that antibiotic adaptation can partly be achieved without gain of novel function. By using knowledge on antibiotic properties, we examined the determinants of cross-resistance and identified chemogenomic profile similarity between antibiotics as the strongest predictor. In contrast, cross-resistance between two antibiotics is independent of whether they show synergistic effects in combination. These results have important implications on the development of novel antimicrobial strategies.

PMID:
25000950
PMCID:
PMC4102323
DOI:
10.1038/ncomms5352
[Indexed for MEDLINE]
Free PMC Article

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