Universität zu Köln

Qi, Qin ORCID: 0000-0002-6148-2416, Angermayr, S. Andreas and Bollenbach, Tobias (2021). Uncovering Key Metabolic Determinants of the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia coli. Front. Microbiol., 12. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-302X

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Abstract

Understanding interactions between antibiotics used in combination is an important theme in microbiology. Using the interactions between the antifolate drug trimethoprim and the ribosome-targeting antibiotic erythromycin in Escherichia coli as a model, we applied a transcriptomic approach for dissecting interactions between two antibiotics with different modes of action. When trimethoprim and erythromycin were combined, the transcriptional response of genes from the sulfate reduction pathway deviated from the dominant effect of trimethoprim on the transcriptome. We successfully altered the drug interaction from additivity to suppression by increasing the sulfate level in the growth environment and identified sulfate reduction as an important metabolic determinant that shapes the interaction between the two drugs. Our work highlights the potential of using prioritization of gene expression patterns as a tool for identifying key metabolic determinants that shape drug-drug interactions. We further demonstrated that the sigma factor-binding protein gene crl shapes the interactions between the two antibiotics, which provides a rare example of how naturally occurring variations between strains of the same bacterial species can sometimes generate very different drug interactions.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Qi, Qin UNSPECIFIED orcid.org/0000-0002-6148-2416 UNSPECIFIED Angermayr, S. Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Bollenbach, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-587572
DOI:	10.3389/fmicb.2021.760017
Journal or Publication Title:	Front. Microbiol.
Volume:	12
Date:	2021
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-302X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ANTIBIOTIC INTERACTIONS; MACROLIDE ANTIBIOTICS; STRINGENT RESPONSE; WILD-TYPE; GENE; SULFUR; EXPRESSION; PROTEIN; STRESS; CRL Multiple languages Microbiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58757