--- res: bibo_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.@eng bibo_authorlist: - foaf_Person: foaf_givenName: Qin foaf_name: Qi, Qin foaf_surname: Qi foaf_workInfoHomepage: http://www.librecat.org/personId=3B22D412-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0002-6148-2416 - foaf_Person: foaf_givenName: S. Andreas foaf_name: Angermayr, S. Andreas foaf_surname: Angermayr - foaf_Person: foaf_givenName: Mark Tobias foaf_name: Bollenbach, Mark Tobias foaf_surname: Bollenbach foaf_workInfoHomepage: http://www.librecat.org/personId=3E6DB97A-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0003-4398-476X bibo_doi: 10.3389/fmicb.2021.760017 bibo_volume: 12 dct_date: 2021^xs_gYear dct_identifier: - UT:000715997300001 dct_isPartOf: - http://id.crossref.org/issn/1664-302X dct_language: eng dct_publisher: Frontiers@ dct_subject: - microbiology dct_title: Uncovering Key Metabolic Determinants of the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia coli@ fabio_hasPubmedId: '34745067' ...