--- _id: '10271' abstract: - lang: eng text: 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. acknowledgement: High-throughput sequencing data were generated by the Vienna BioCenter Core Facilities. The authors would like to thank Karin Mitosch, Bor Kavcic, and Nadine Kraupner for their constructive feedback. The authors would also like to thank Gertraud Stift, Julia Flor, Renate Srsek, Agnieszka Wiktor, and Booshini Fernando for technical support. article_number: '760017' article_processing_charge: No article_type: original author: - first_name: Qin full_name: Qi, Qin id: 3B22D412-F248-11E8-B48F-1D18A9856A87 last_name: Qi orcid: 0000-0002-6148-2416 - first_name: S. Andreas full_name: Angermayr, S. Andreas last_name: Angermayr - first_name: Mark Tobias full_name: Bollenbach, Mark Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X citation: ama: Qi Q, Angermayr SA, Bollenbach MT. Uncovering Key Metabolic Determinants of the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia coli. Frontiers in Microbiology. 2021;12. doi:10.3389/fmicb.2021.760017 apa: Qi, Q., Angermayr, S. A., & Bollenbach, M. T. (2021). Uncovering Key Metabolic Determinants of the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia coli. Frontiers in Microbiology. Frontiers. https://doi.org/10.3389/fmicb.2021.760017 chicago: Qi, Qin, S. Andreas Angermayr, and Mark Tobias Bollenbach. “Uncovering Key Metabolic Determinants of the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia Coli.” Frontiers in Microbiology. Frontiers, 2021. https://doi.org/10.3389/fmicb.2021.760017. ieee: Q. Qi, S. A. Angermayr, and M. T. Bollenbach, “Uncovering Key Metabolic Determinants of the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia coli,” Frontiers in Microbiology, vol. 12. Frontiers, 2021. ista: Qi Q, Angermayr SA, Bollenbach MT. 2021. Uncovering Key Metabolic Determinants of the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia coli. Frontiers in Microbiology. 12, 760017. mla: Qi, Qin, et al. “Uncovering Key Metabolic Determinants of the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia Coli.” Frontiers in Microbiology, vol. 12, 760017, Frontiers, 2021, doi:10.3389/fmicb.2021.760017. short: Q. Qi, S.A. Angermayr, M.T. Bollenbach, Frontiers in Microbiology 12 (2021). date_created: 2021-11-11T10:39:37Z date_published: 2021-10-20T00:00:00Z date_updated: 2023-08-14T11:43:23Z day: '20' ddc: - '610' doi: 10.3389/fmicb.2021.760017 ec_funded: 1 external_id: isi: - '000715997300001' pmid: - '34745067' file: - access_level: open_access checksum: d41321748e9588dd3cf03e9a7222127f content_type: application/pdf creator: cchlebak date_created: 2021-11-11T10:54:40Z date_updated: 2021-11-11T10:54:40Z file_id: '10272' file_name: 2021_FrontiersMicrob_Qi.pdf file_size: 2397203 relation: main_file success: 1 file_date_updated: 2021-11-11T10:54:40Z has_accepted_license: '1' intvolume: ' 12' isi: 1 keyword: - microbiology language: - iso: eng month: '10' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 25E9AF9E-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P27201-B22 name: Revealing the mechanisms underlying drug interactions - _id: 25E83C2C-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '303507' name: Optimality principles in responses to antibiotics publication: Frontiers in Microbiology publication_identifier: eissn: - 1664-302X publication_status: published publisher: Frontiers quality_controlled: '1' scopus_import: '1' status: public title: Uncovering Key Metabolic Determinants of the Drug Interactions Between Trimethoprim and Erythromycin in Escherichia coli tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 12 year: '2021' ...