--- _id: '10812' abstract: - lang: eng text: Several promising strategies based on combining or cycling different antibiotics have been proposed to increase efficacy and counteract resistance evolution, but we still lack a deep understanding of the physiological responses and genetic mechanisms that underlie antibiotic interactions and the clinical applicability of these strategies. In antibiotic-exposed bacteria, the combined effects of physiological stress responses and emerging resistance mutations (occurring at different time scales) generate complex and often unpredictable dynamics. In this Review, we present our current understanding of bacterial cell physiology and genetics of responses to antibiotics. We emphasize recently discovered mechanisms of synergistic and antagonistic drug interactions, hysteresis in temporal interactions between antibiotics that arise from microbial physiology and interactions between antibiotics and resistance mutations that can cause collateral sensitivity or cross-resistance. We discuss possible connections between the different phenomena and indicate relevant research directions. A better and more unified understanding of drug and genetic interactions is likely to advance antibiotic therapy. acknowledgement: The authors thank B. Kavčič and H. Schulenburg for constructive feedback on the manuscript. article_processing_charge: No article_type: review author: - first_name: Roderich full_name: Römhild, Roderich id: 68E56E44-62B0-11EA-B963-444F3DDC885E last_name: Römhild orcid: 0000-0001-9480-5261 - first_name: Mark Tobias full_name: Bollenbach, Mark Tobias id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87 last_name: Bollenbach orcid: 0000-0003-4398-476X - first_name: Dan I. full_name: Andersson, Dan I. last_name: Andersson citation: ama: Römhild R, Bollenbach MT, Andersson DI. The physiology and genetics of bacterial responses to antibiotic combinations. Nature Reviews Microbiology. 2022;20:478-490. doi:10.1038/s41579-022-00700-5 apa: Römhild, R., Bollenbach, M. T., & Andersson, D. I. (2022). The physiology and genetics of bacterial responses to antibiotic combinations. Nature Reviews Microbiology. Springer Nature. https://doi.org/10.1038/s41579-022-00700-5 chicago: Römhild, Roderich, Mark Tobias Bollenbach, and Dan I. Andersson. “The Physiology and Genetics of Bacterial Responses to Antibiotic Combinations.” Nature Reviews Microbiology. Springer Nature, 2022. https://doi.org/10.1038/s41579-022-00700-5. ieee: R. Römhild, M. T. Bollenbach, and D. I. Andersson, “The physiology and genetics of bacterial responses to antibiotic combinations,” Nature Reviews Microbiology, vol. 20. Springer Nature, pp. 478–490, 2022. ista: Römhild R, Bollenbach MT, Andersson DI. 2022. The physiology and genetics of bacterial responses to antibiotic combinations. Nature Reviews Microbiology. 20, 478–490. mla: Römhild, Roderich, et al. “The Physiology and Genetics of Bacterial Responses to Antibiotic Combinations.” Nature Reviews Microbiology, vol. 20, Springer Nature, 2022, pp. 478–90, doi:10.1038/s41579-022-00700-5. short: R. Römhild, M.T. Bollenbach, D.I. Andersson, Nature Reviews Microbiology 20 (2022) 478–490. date_created: 2022-03-04T04:33:49Z date_published: 2022-08-01T00:00:00Z date_updated: 2023-08-02T14:41:44Z day: '01' department: - _id: CaGu doi: 10.1038/s41579-022-00700-5 external_id: isi: - '000763891900001' pmid: - '35241807' intvolume: ' 20' isi: 1 keyword: - General Immunology and Microbiology - Microbiology - Infectious Diseases language: - iso: eng month: '08' oa_version: None page: 478-490 pmid: 1 publication: Nature Reviews Microbiology publication_identifier: eissn: - 1740-1534 issn: - 1740-1526 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: The physiology and genetics of bacterial responses to antibiotic combinations type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 20 year: '2022' ...