[{"acknowledgement":"We are very grateful to S. Hernando-Amado (Madrid, Spain), C. Pál (Szeged, Hungary), and T. Bollenbach (Cologne, Germany) for critical comments and advice on the manuscript. We further thank D. Rogers, J. Summers (Ploen, Germany) for guidance in allelic exchange, P. Rainey (Ploen, Germany) for providing the plasmids and strains, then J. Lorenzen, K. Flinder, N. Steinbach, S. Butze (all Schulenburg lab), and L. Kirchhoff (Rupp lab) for supporting the experimental work, and also the Rupp and Schulenburg groups for general feedback. We are grateful for financial support from the German Research Foundation within the Research and Training Group 2501 (RTG 2501) on Translational Evolutionary Research (project 4.2 to H.S.), within the Excellence cluster Precision Medicine in chronic Inflammation (PMI; funding under Germany’s Excellence Strategy EXC 2167-390884018, to B.K., K.R., J.R., H.S.), within the Clinician Scientist Program in Evolutionary Medicine (CSEM) – project number 413490537 (to EEG), and as part of the individual grants SCHU 1415/12-2 (to H.S.) and BR-2915/7-1 (to M.B.). We are grateful for financial support from the Swedish Research Council, project number 2021-02091 (to D.I.A.). We are also grateful for financial support from the Max-Planck Society (Fellowship to H.S.), the Leibniz Association within the Leibniz Science-Campus Evolutionary Medicine of the Lung (EvoLUNG, to H.S.), and the project SKILLED funded by the DAMP foundation (to J.R., H.S.). This work was also supported by the ZMB Young Scientist award and the FWF grant 10.55776/ESP219 (to R.R.) and the TransEvo Innovation prize (to F.B.). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Open Access funding enabled and organized by Projekt DEAL.\r\n","type":"journal_article","OA_place":"publisher","volume":17,"publication_identifier":{"eissn":["2041-1723"]},"status":"public","oa":1,"year":"2026","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"file":[{"date_created":"2026-06-02T07:11:12Z","relation":"main_file","date_updated":"2026-06-02T07:11:12Z","file_name":"2026_NatureComm_Buchholz.pdf","file_size":1276166,"content_type":"application/pdf","checksum":"aa29f8806908dc0469dff21e2d5ad01f","file_id":"21936","access_level":"open_access","creator":"dernst","success":1}],"language":[{"iso":"eng"}],"has_accepted_license":"1","PlanS_conform":"1","doi":"10.1038/s41467-026-71178-5","month":"05","DOAJ_listed":"1","article_type":"original","scopus_import":"1","department":[{"_id":"CaGu"}],"intvolume":"        17","day":"20","oa_version":"Published Version","article_processing_charge":"Yes (via OA deal)","_id":"21928","quality_controlled":"1","citation":{"apa":"Buchholz, F., Upterworth, L. M., Tueffers, L., Groth, E. E., Haas, K., Schütz, D., … Schulenburg, H. (2026). Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-026-71178-5\">https://doi.org/10.1038/s41467-026-71178-5</a>","ama":"Buchholz F, Upterworth LM, Tueffers L, et al. Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope. <i>Nature Communications</i>. 2026;17. doi:<a href=\"https://doi.org/10.1038/s41467-026-71178-5\">10.1038/s41467-026-71178-5</a>","chicago":"Buchholz, Florian, Lina M. Upterworth, Leif Tueffers, Espen E. Groth, Kira Haas, Daniel Schütz, Abigail Savietto Scholz, et al. “Robust Antibiotic Sensitization of Pathogenic Pseudomonas Aeruginosa via Negative Hysteresis in the Cell Envelope.” <i>Nature Communications</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41467-026-71178-5\">https://doi.org/10.1038/s41467-026-71178-5</a>.","ista":"Buchholz F, Upterworth LM, Tueffers L, Groth EE, Haas K, Schütz D, Savietto Scholz A, Batra A, Pal S, Banerjee S, Dubey BN, Franzenburg S, Kalsdorf B, Rabe KF, Nurjadi D, Rupp J, Andersson DI, Sondermann H, Bramkamp M, Römhild R, Schulenburg H. 2026. Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope. Nature Communications. 17, 4487.","mla":"Buchholz, Florian, et al. “Robust Antibiotic Sensitization of Pathogenic Pseudomonas Aeruginosa via Negative Hysteresis in the Cell Envelope.” <i>Nature Communications</i>, vol. 17, 4487, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s41467-026-71178-5\">10.1038/s41467-026-71178-5</a>.","short":"F. Buchholz, L.M. Upterworth, L. Tueffers, E.E. Groth, K. Haas, D. Schütz, A. Savietto Scholz, A. Batra, S. Pal, S. Banerjee, B.N. Dubey, S. Franzenburg, B. Kalsdorf, K.F. Rabe, D. Nurjadi, J. Rupp, D.I. Andersson, H. Sondermann, M. Bramkamp, R. Römhild, H. Schulenburg, Nature Communications 17 (2026).","ieee":"F. Buchholz <i>et al.</i>, “Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope,” <i>Nature Communications</i>, vol. 17. Springer Nature, 2026."},"ddc":["570"],"publisher":"Springer Nature","publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication":"Nature Communications","file_date_updated":"2026-06-02T07:11:12Z","date_published":"2026-05-20T00:00:00Z","OA_type":"gold","corr_author":"1","article_number":"4487","project":[{"_id":"bd6f94d1-d553-11ed-ba76-ae9f07250f74","name":"Non-canonical antibiotic interactions","grant_number":"E219"}],"title":"Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope","author":[{"first_name":"Florian","last_name":"Buchholz","full_name":"Buchholz, Florian"},{"last_name":"Upterworth","first_name":"Lina M.","full_name":"Upterworth, Lina M."},{"full_name":"Tueffers, Leif","last_name":"Tueffers","first_name":"Leif"},{"full_name":"Groth, Espen E.","last_name":"Groth","first_name":"Espen E."},{"first_name":"Kira","last_name":"Haas","full_name":"Haas, Kira"},{"first_name":"Daniel","last_name":"Schütz","full_name":"Schütz, Daniel"},{"full_name":"Savietto Scholz, Abigail","last_name":"Savietto Scholz","first_name":"Abigail"},{"last_name":"Batra","first_name":"Aditi","full_name":"Batra, Aditi"},{"last_name":"Pal","first_name":"Surajit","full_name":"Pal, Surajit"},{"first_name":"Samarpita","last_name":"Banerjee","full_name":"Banerjee, Samarpita"},{"full_name":"Dubey, Badri N.","first_name":"Badri N.","last_name":"Dubey"},{"first_name":"Sören","last_name":"Franzenburg","full_name":"Franzenburg, Sören"},{"full_name":"Kalsdorf, Barbara","first_name":"Barbara","last_name":"Kalsdorf"},{"last_name":"Rabe","first_name":"Klaus F.","full_name":"Rabe, Klaus F."},{"first_name":"Dennis","last_name":"Nurjadi","full_name":"Nurjadi, Dennis"},{"last_name":"Rupp","first_name":"Jan","full_name":"Rupp, Jan"},{"full_name":"Andersson, Dan I.","last_name":"Andersson","first_name":"Dan I."},{"full_name":"Sondermann, Holger","first_name":"Holger","last_name":"Sondermann"},{"full_name":"Bramkamp, Marc","first_name":"Marc","last_name":"Bramkamp"},{"full_name":"Römhild, Roderich","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","orcid":"0000-0001-9480-5261","first_name":"Roderich","last_name":"Römhild"},{"first_name":"Hinrich","last_name":"Schulenburg","full_name":"Schulenburg, Hinrich"}],"date_created":"2026-05-31T22:02:12Z","date_updated":"2026-06-02T07:14:35Z","abstract":[{"text":"Antibiotic combination in time and space is a key strategy to combat antimicrobial resistance. The success of such treatment designs requires their robust efficacy across treatment conditions and a pathogen’s genomic diversity. This study found that an initial treatment with a β-lactam antibiotic causes robust cellular sensitization towards an aminoglycoside antibiotic across the high-risk human pathogen Pseudomonas aeruginosa, including resistant strains. This phenomenon of cellular sensitization, termed negative hysteresis, is modulated by the Cpx envelope stress response system and linked to membrane stress during growth. The increase in efficacy is achieved through a β-lactam induced elevated cellular uptake of the subsequently administered aminoglycoside. Negative hysteresis and the Cpx system are linked in several cases to the expression of synergistic drug interactions, thus enhancing efficacy of antibiotic combinations. Overall, our study identifies the phenomenon of negative hysteresis as a robustly inducible phenotype and thus a unique focus for optimizing antimicrobial therapy.","lang":"eng"}]},{"type":"journal_article","APC_amount":"5949 EUR","acknowledgement":"K.J. thanks B. Wu, I. Tomanek, K. Tomasek for detailed discussions on the manuscript, all other members from the Guet laboratory for valuable feedback, R. Chait, & Imaging and Optics Facility, Institute of Science and Technology Austria for helping with microscopy, Dr. Sudha Rao and Dr. Raja Mugasimangalam, Genotypic Technology India for allowing time off to address the revisions. K.J. acknowledges Institute of Science and Technology fellowship IC1006FELL02, R.H. was supported in part by Chan Zuckerberg Initiative and Donor Advised-Fund grant 2020-225401 (https://doi.org/10.37921/120055ratwvi), O.O.B. acknowledges Fonds Zur Förderung der Wissenschaftlichen Forschung (FWF) Grant ESP253-B, R.R. acknowledges FWF Grant 10.55776/ESP219, C.C.G. acknowledges FWF I5127-B.","status":"public","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"volume":122,"OA_place":"publisher","issue":"15","doi":"10.1073/pnas.2413709122","related_material":{"record":[{"status":"public","id":"19294","relation":"research_data"}],"link":[{"url":"https://ista.ac.at/en/news/clockwork-just-for-antibiotic-resistance/","description":"News on ISTA website","relation":"press_release"}]},"has_accepted_license":"1","language":[{"iso":"eng"}],"file":[{"relation":"main_file","date_created":"2025-06-24T07:27:43Z","file_size":2949523,"content_type":"application/pdf","checksum":"115a687f40009660eb4b38b4f6559d41","file_name":"2025_PNAS_Jain.pdf","date_updated":"2025-06-24T07:27:43Z","file_id":"19888","success":1,"creator":"dernst","access_level":"open_access"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"year":"2025","oa":1,"isi":1,"month":"04","_id":"19626","oa_version":"Published Version","article_processing_charge":"Yes (in subscription journal)","day":"15","intvolume":"       122","department":[{"_id":"CaGu"},{"_id":"Bio"},{"_id":"FyKo"},{"_id":"GaTk"}],"scopus_import":"1","article_type":"original","publisher":"National Academy of Sciences","acknowledged_ssus":[{"_id":"Bio"}],"ddc":["570"],"citation":{"ama":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. Pulsatile basal gene expression as a fitness determinant in bacteria. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(15). doi:<a href=\"https://doi.org/10.1073/pnas.2413709122\">10.1073/pnas.2413709122</a>","apa":"Jain, K., Hauschild, R., Bochkareva, O., Römhild, R., Tkačik, G., &#38; Guet, C. C. (2025). Pulsatile basal gene expression as a fitness determinant in bacteria. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2413709122\">https://doi.org/10.1073/pnas.2413709122</a>","chicago":"Jain, Kirti, Robert Hauschild, Olga Bochkareva, Roderich Römhild, Gašper Tkačik, and Calin C Guet. “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2413709122\">https://doi.org/10.1073/pnas.2413709122</a>.","ista":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. 2025. Pulsatile basal gene expression as a fitness determinant in bacteria. Proceedings of the National Academy of Sciences. 122(15), e2413709122.","short":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, Proceedings of the National Academy of Sciences 122 (2025).","mla":"Jain, Kirti, et al. “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 15, e2413709122, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2413709122\">10.1073/pnas.2413709122</a>.","ieee":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, and C. C. Guet, “Pulsatile basal gene expression as a fitness determinant in bacteria,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 15. National Academy of Sciences, 2025."},"quality_controlled":"1","article_number":"e2413709122","corr_author":"1","OA_type":"hybrid","date_published":"2025-04-15T00:00:00Z","file_date_updated":"2025-06-24T07:27:43Z","publication":"Proceedings of the National Academy of Sciences","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_status":"published","pmid":1,"abstract":[{"lang":"eng","text":"Active regulation of gene expression, orchestrated by complex interactions of activators and repressors at promoters, controls the fate of organisms. In contrast, basal expression at uninduced promoters is considered to be a dynamically inert mode of nonfunctional “promoter leakiness,” merely a byproduct of transcriptional regulation. Here, we investigate the basal expression mode of the mar operon, the main regulator of intrinsic multiple antibiotic resistance in Escherichia coli, and link its dynamic properties to the noncanonical, yet highly conserved start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements across tens of generations reveal that basal expression consists of rare stochastic gene expression pulses, which maximize variability in wildtype and, surprisingly, transiently accelerate cellular elongation rates. Competition experiments show that basal expression confers fitness advantages to wildtype across several transitions between exponential and stationary growth by shortening lag times. The dynamically rich basal expression of the mar operon has likely been evolutionarily maintained for its role in growth homeostasis of Enterobacteria within the gut environment, thereby allowing other ancillary gene regulatory roles to evolve, e.g., control of costly-to-induce multidrug efflux pumps. Understanding the complex selection forces governing genetic systems involved in intrinsic multidrug resistance is crucial for effective public health measures."}],"date_updated":"2026-05-20T08:33:08Z","date_created":"2025-04-27T22:02:13Z","external_id":{"isi":["001471235200001"],"pmid":["40193613"]},"author":[{"orcid":"0000-0002-3809-0449","last_name":"Jain","first_name":"Kirti","full_name":"Jain, Kirti","id":"330F0278-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert","last_name":"Hauschild","orcid":"0000-0001-9843-3522"},{"first_name":"Olga","last_name":"Bochkareva","orcid":"0000-0003-1006-6639","id":"C4558D3C-6102-11E9-A62E-F418E6697425","full_name":"Bochkareva, Olga"},{"full_name":"Römhild, Roderich","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","orcid":"0000-0001-9480-5261","first_name":"Roderich","last_name":"Römhild"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","last_name":"Tkačik","first_name":"Gašper"},{"orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"title":"Pulsatile basal gene expression as a fitness determinant in bacteria","project":[{"name":"Tools for automation and feedback microscopy","grant_number":"CZI01","_id":"c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473"},{"_id":"bd6f94d1-d553-11ed-ba76-ae9f07250f74","name":"Non-canonical antibiotic interactions","grant_number":"E219"},{"_id":"34e076d6-11ca-11ed-8bc3-aec76c41a181","grant_number":"I05127","name":"Evolutionary analysis of gene regulation"}]},{"date_published":"2025-03-04T00:00:00Z","OA_type":"gold","corr_author":"1","related_material":{"record":[{"id":"19626","status":"public","relation":"used_in_publication"}]},"has_accepted_license":"1","doi":"10.15479/AT:ISTA:19294","oa":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2025","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"file":[{"access_level":"open_access","creator":"dernst","success":1,"file_id":"19295","file_name":"Data1.xlsx","date_updated":"2025-03-04T13:08:52Z","file_size":269054,"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","checksum":"11a5bab307a4e1e1598a1577d8a2fbb5","date_created":"2025-03-04T13:08:52Z","relation":"main_file"},{"date_updated":"2025-03-04T13:08:52Z","file_name":"Data2.xlsx","file_size":87143,"checksum":"3b057894322639f0c1e11fb2e84173e6","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","date_created":"2025-03-04T13:08:52Z","relation":"main_file","access_level":"open_access","creator":"dernst","success":1,"file_id":"19296"},{"date_created":"2025-03-04T13:08:52Z","relation":"main_file","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","checksum":"a551e1b79a138bb97ab96979aa475b3c","file_size":129101,"file_name":"Data3.xlsx","date_updated":"2025-03-04T13:08:52Z","file_id":"19297","access_level":"open_access","success":1,"creator":"dernst"},{"creator":"dernst","success":1,"access_level":"open_access","file_id":"19298","date_updated":"2025-03-04T13:08:52Z","file_name":"Data4.xlsx","file_size":86243,"checksum":"d6909c9bf111f859058082b1a2f970c4","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","relation":"main_file","date_created":"2025-03-04T13:08:52Z"},{"relation":"main_file","date_created":"2025-03-04T13:08:52Z","file_name":"Data5.xlsx","date_updated":"2025-03-04T13:08:52Z","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","file_size":26049,"checksum":"e5725a3a118a3f06846104906c8792c7","file_id":"19299","creator":"dernst","success":1,"access_level":"open_access"},{"file_id":"19300","access_level":"open_access","success":1,"creator":"dernst","date_created":"2025-03-04T13:08:52Z","relation":"main_file","checksum":"16763c127049f14bd587dc885677dce1","file_size":7327253,"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","date_updated":"2025-03-04T13:08:52Z","file_name":"RawData_2_3.xlsx"},{"file_id":"19301","creator":"dernst","success":1,"access_level":"open_access","relation":"main_file","date_created":"2025-03-05T07:39:38Z","file_name":"Readme.txt","date_updated":"2025-03-05T07:39:38Z","content_type":"text/plain","file_size":606,"checksum":"2f3e1a368b4e3abc46bf37e02724f0f4"}],"file_date_updated":"2025-03-05T07:39:38Z","date_updated":"2026-05-20T08:33:07Z","abstract":[{"text":"Active regulation of gene expression, orchestrated by complex interactions of activators and repressors at promoters, controls the fate of organisms. In contrast, basal expression at uninduced promoters is considered to be a dynamically inert mode of non-functional “promoter leakiness”, merely a byproduct of transcriptional regulation. Here, we investigate the basal expression mode of the mar operon, the main regulator of intrinsic multiple antibiotic resistance in Escherichia coli, and link its dynamic properties to the non-canonical, yet highly conserved start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements across tens of generations reveal that basal expression consists of rare stochastic gene expression pulses, which maximize variability in wildtype and, surprisingly, transiently accelerate cellular elongation rates. Competition experiments show that basal expression confers fitness advantages to wildtype across several transitions between exponential and stationary growth by shortening lag times. The dynamically rich basal expression of the mar operon has likely been evolutionarily maintained for its role in growth homeostasis of Enterobacteria within the gut environment, thereby allowing other ancillary gene regulatory roles to evolve, e.g. control of costly-to-induce multi-drug efflux pumps. Understanding the complex selection forces governing genetic systems involved in intrinsic multi-drug resistance is crucial for effective public health measures.","lang":"eng"}],"month":"03","title":"Data for \"Pulsatile basal gene expression as a fitness determinant in bacteria\"","author":[{"full_name":"Jain, Kirti","id":"330F0278-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3809-0449","first_name":"Kirti","last_name":"Jain"},{"first_name":"Robert","last_name":"Hauschild","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert"},{"id":"C4558D3C-6102-11E9-A62E-F418E6697425","full_name":"Bochkareva, Olga","first_name":"Olga","last_name":"Bochkareva","orcid":"0000-0003-1006-6639"},{"id":"68E56E44-62B0-11EA-B963-444F3DDC885E","full_name":"Römhild, Roderich","orcid":"0000-0001-9480-5261","first_name":"Roderich","last_name":"Römhild"},{"orcid":"0000-0002-6699-1455","last_name":"Tkačik","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet","first_name":"Calin C"}],"date_created":"2025-03-04T13:27:21Z","day":"04","article_processing_charge":"No","oa_version":"Published Version","type":"research_data","_id":"19294","department":[{"_id":"CaGu"},{"_id":"Bio"},{"_id":"FyKo"},{"_id":"GaTk"}],"publisher":"Institute of Science and Technology Austria","status":"public","OA_place":"repository","citation":{"chicago":"Jain, Kirti, Robert Hauschild, Olga Bochkareva, Roderich Römhild, Gašper Tkačik, and Calin C Guet. “Data for ‘Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.’” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT:ISTA:19294\">https://doi.org/10.15479/AT:ISTA:19294</a>.","ama":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. Data for “Pulsatile basal gene expression as a fitness determinant in bacteria.” 2025. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:19294\">10.15479/AT:ISTA:19294</a>","apa":"Jain, K., Hauschild, R., Bochkareva, O., Römhild, R., Tkačik, G., &#38; Guet, C. C. (2025). Data for “Pulsatile basal gene expression as a fitness determinant in bacteria.” Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:19294\">https://doi.org/10.15479/AT:ISTA:19294</a>","ieee":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, and C. C. Guet, “Data for ‘Pulsatile basal gene expression as a fitness determinant in bacteria.’” Institute of Science and Technology Austria, 2025.","short":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, (2025).","mla":"Jain, Kirti, et al. <i>Data for “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.”</i> Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:19294\">10.15479/AT:ISTA:19294</a>.","ista":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. 2025. Data for ‘Pulsatile basal gene expression as a fitness determinant in bacteria’, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:19294\">10.15479/AT:ISTA:19294</a>."},"ddc":["570"]},{"doi":"10.1038/s41579-022-00700-5","page":"478-490","language":[{"iso":"eng"}],"year":"2022","isi":1,"month":"08","type":"journal_article","acknowledgement":"The authors thank B. Kavčič and H. Schulenburg for constructive feedback on the manuscript.","status":"public","publication_identifier":{"issn":["1740-1526"],"eissn":["1740-1534"]},"keyword":["General Immunology and Microbiology","Microbiology","Infectious Diseases"],"volume":20,"date_published":"2022-08-01T00:00:00Z","publication":"Nature Reviews Microbiology","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","pmid":1,"publication_status":"published","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."}],"date_updated":"2023-08-02T14:41:44Z","date_created":"2022-03-04T04:33:49Z","external_id":{"isi":["000763891900001"],"pmid":["35241807"]},"author":[{"orcid":"0000-0001-9480-5261","last_name":"Römhild","first_name":"Roderich","full_name":"Römhild, Roderich","id":"68E56E44-62B0-11EA-B963-444F3DDC885E"},{"full_name":"Bollenbach, Mark Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4398-476X","last_name":"Bollenbach","first_name":"Mark Tobias"},{"full_name":"Andersson, Dan I.","last_name":"Andersson","first_name":"Dan I."}],"title":"The physiology and genetics of bacterial responses to antibiotic combinations","_id":"10812","oa_version":"None","article_processing_charge":"No","day":"01","intvolume":"        20","department":[{"_id":"CaGu"}],"article_type":"review","scopus_import":"1","publisher":"Springer Nature","quality_controlled":"1","citation":{"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.” <i>Nature Reviews Microbiology</i>, vol. 20, Springer Nature, 2022, pp. 478–90, doi:<a href=\"https://doi.org/10.1038/s41579-022-00700-5\">10.1038/s41579-022-00700-5</a>.","short":"R. Römhild, M.T. Bollenbach, D.I. Andersson, Nature Reviews Microbiology 20 (2022) 478–490.","ieee":"R. Römhild, M. T. Bollenbach, and D. I. Andersson, “The physiology and genetics of bacterial responses to antibiotic combinations,” <i>Nature Reviews Microbiology</i>, vol. 20. Springer Nature, pp. 478–490, 2022.","ama":"Römhild R, Bollenbach MT, Andersson DI. The physiology and genetics of bacterial responses to antibiotic combinations. <i>Nature Reviews Microbiology</i>. 2022;20:478-490. doi:<a href=\"https://doi.org/10.1038/s41579-022-00700-5\">10.1038/s41579-022-00700-5</a>","apa":"Römhild, R., Bollenbach, M. T., &#38; Andersson, D. I. (2022). The physiology and genetics of bacterial responses to antibiotic combinations. <i>Nature Reviews Microbiology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41579-022-00700-5\">https://doi.org/10.1038/s41579-022-00700-5</a>","chicago":"Römhild, Roderich, Mark Tobias Bollenbach, and Dan I. Andersson. “The Physiology and Genetics of Bacterial Responses to Antibiotic Combinations.” <i>Nature Reviews Microbiology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41579-022-00700-5\">https://doi.org/10.1038/s41579-022-00700-5</a>."}},{"month":"01","isi":1,"oa":1,"year":"2021","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"language":[{"iso":"eng"}],"file":[{"relation":"main_file","date_created":"2021-02-03T12:13:03Z","date_updated":"2021-02-03T12:13:03Z","file_name":"2021_PlosPathogens_Roemhild.pdf","checksum":"d745d7f8fcbb9b95fea16a36f94dee31","file_size":570066,"content_type":"application/pdf","file_id":"9070","creator":"dernst","success":1,"access_level":"open_access"}],"has_accepted_license":"1","issue":"1","doi":"10.1371/journal.ppat.1009172","volume":17,"publication_identifier":{"issn":["1553-7366"],"eissn":["1553-7374"]},"status":"public","acknowledgement":"Our work was supported by the Swedish Research Council (grant 2017-01527) to DIA","type":"journal_article","title":"Mechanisms and therapeutic potential of collateral sensitivity to antibiotics","author":[{"id":"68E56E44-62B0-11EA-B963-444F3DDC885E","full_name":"Römhild, Roderich","first_name":"Roderich","last_name":"Römhild","orcid":"0000-0001-9480-5261"},{"full_name":"Andersson, Dan I.","last_name":"Andersson","first_name":"Dan I."}],"external_id":{"pmid":["33444399"],"isi":["000610190400007"]},"date_created":"2021-01-31T23:01:21Z","date_updated":"2025-07-10T12:01:33Z","publication_status":"published","pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication":"PLoS Pathogens","file_date_updated":"2021-02-03T12:13:03Z","date_published":"2021-01-14T00:00:00Z","article_number":"e1009172","citation":{"ista":"Römhild R, Andersson DI. 2021. Mechanisms and therapeutic potential of collateral sensitivity to antibiotics. PLoS Pathogens. 17(1), e1009172.","ieee":"R. Römhild and D. I. Andersson, “Mechanisms and therapeutic potential of collateral sensitivity to antibiotics,” <i>PLoS Pathogens</i>, vol. 17, no. 1. Public Library of Science, 2021.","short":"R. Römhild, D.I. Andersson, PLoS Pathogens 17 (2021).","mla":"Römhild, Roderich, and Dan I. Andersson. “Mechanisms and Therapeutic Potential of Collateral Sensitivity to Antibiotics.” <i>PLoS Pathogens</i>, vol. 17, no. 1, e1009172, Public Library of Science, 2021, doi:<a href=\"https://doi.org/10.1371/journal.ppat.1009172\">10.1371/journal.ppat.1009172</a>.","apa":"Römhild, R., &#38; Andersson, D. I. (2021). Mechanisms and therapeutic potential of collateral sensitivity to antibiotics. <i>PLoS Pathogens</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.ppat.1009172\">https://doi.org/10.1371/journal.ppat.1009172</a>","ama":"Römhild R, Andersson DI. Mechanisms and therapeutic potential of collateral sensitivity to antibiotics. <i>PLoS Pathogens</i>. 2021;17(1). doi:<a href=\"https://doi.org/10.1371/journal.ppat.1009172\">10.1371/journal.ppat.1009172</a>","chicago":"Römhild, Roderich, and Dan I. Andersson. “Mechanisms and Therapeutic Potential of Collateral Sensitivity to Antibiotics.” <i>PLoS Pathogens</i>. Public Library of Science, 2021. <a href=\"https://doi.org/10.1371/journal.ppat.1009172\">https://doi.org/10.1371/journal.ppat.1009172</a>."},"quality_controlled":"1","ddc":["570"],"publisher":"Public Library of Science","scopus_import":"1","article_type":"original","department":[{"_id":"CaGu"}],"intvolume":"        17","day":"14","article_processing_charge":"No","oa_version":"Published Version","_id":"9046"},{"volume":10,"publication_identifier":{"eissn":["2050-084X"]},"status":"public","acknowledgement":"We would like to thank Leif Tueffers and João Botelho for discussions and suggestions as well as Kira Haas and Julia Bunk for technical support. We acknowledge financial support from the German Science Foundation (grant SCHU 1415/12-2 to HS, and funding under Germany’s Excellence Strategy EXC 2167–390884018 as well as the Research Training Group 2501 TransEvo to HS and SN), the Max Planck Society (IMPRS scholarship to AB; Max-Planck fellowship to HS), and the Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG, to HS and SN). This work was further supported by the German Science Foundation Research Infrastructure NGS_CC (project 407495230) as part of the Next Generation Sequencing Competence Network (project 423957469). NGS analyses were carried out at the Competence Centre for Genomic Analysis Kiel (CCGA Kiel).","type":"journal_article","month":"07","isi":1,"oa":1,"year":"2021","language":[{"iso":"eng"}],"doi":"10.7554/elife.68876","quality_controlled":"1","citation":{"ista":"Batra A, Römhild R, Rousseau E, Franzenburg S, Niemann S, Schulenburg H. 2021. High potency of sequential therapy with only beta-lactam antibiotics. eLife. 10, e68876.","short":"A. Batra, R. Römhild, E. Rousseau, S. Franzenburg, S. Niemann, H. Schulenburg, ELife 10 (2021).","mla":"Batra, Aditi, et al. “High Potency of Sequential Therapy with Only Beta-Lactam Antibiotics.” <i>ELife</i>, vol. 10, e68876, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/elife.68876\">10.7554/elife.68876</a>.","ieee":"A. Batra, R. Römhild, E. Rousseau, S. Franzenburg, S. Niemann, and H. Schulenburg, “High potency of sequential therapy with only beta-lactam antibiotics,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","ama":"Batra A, Römhild R, Rousseau E, Franzenburg S, Niemann S, Schulenburg H. High potency of sequential therapy with only beta-lactam antibiotics. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/elife.68876\">10.7554/elife.68876</a>","apa":"Batra, A., Römhild, R., Rousseau, E., Franzenburg, S., Niemann, S., &#38; Schulenburg, H. (2021). High potency of sequential therapy with only beta-lactam antibiotics. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.68876\">https://doi.org/10.7554/elife.68876</a>","chicago":"Batra, Aditi, Roderich Römhild, Emilie Rousseau, Sören Franzenburg, Stefan Niemann, and Hinrich Schulenburg. “High Potency of Sequential Therapy with Only Beta-Lactam Antibiotics.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/elife.68876\">https://doi.org/10.7554/elife.68876</a>."},"publisher":"eLife Sciences Publications","article_type":"original","scopus_import":"1","department":[{"_id":"CaGu"}],"intvolume":"        10","day":"28","oa_version":"Published Version","article_processing_charge":"No","_id":"9746","title":"High potency of sequential therapy with only beta-lactam antibiotics","author":[{"first_name":"Aditi","last_name":"Batra","full_name":"Batra, Aditi"},{"full_name":"Römhild, Roderich","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","first_name":"Roderich","last_name":"Römhild","orcid":"0000-0001-9480-5261"},{"last_name":"Rousseau","first_name":"Emilie","full_name":"Rousseau, Emilie"},{"first_name":"Sören","last_name":"Franzenburg","full_name":"Franzenburg, Sören"},{"first_name":"Stefan","last_name":"Niemann","full_name":"Niemann, Stefan"},{"full_name":"Schulenburg, Hinrich","last_name":"Schulenburg","first_name":"Hinrich"}],"external_id":{"pmid":["34318749"],"isi":["000692027800001"]},"date_created":"2021-07-28T13:36:57Z","main_file_link":[{"url":"https://doi.org/10.7554/eLife.68876","open_access":"1"}],"date_updated":"2023-08-11T10:26:29Z","abstract":[{"lang":"eng","text":"Evolutionary adaptation is a major source of antibiotic resistance in bacterial pathogens. Evolution-informed therapy aims to constrain resistance by accounting for bacterial evolvability. Sequential treatments with antibiotics that target different bacterial processes were previously shown to limit adaptation through genetic resistance trade-offs and negative hysteresis. Treatment with homogeneous sets of antibiotics is generally viewed to be disadvantageous, as it should rapidly lead to cross-resistance. We here challenged this assumption by determining the evolutionary response of Pseudomonas aeruginosa to experimental sequential treatments involving both heterogenous and homogeneous antibiotic sets. To our surprise, we found that fast switching between only β-lactam antibiotics resulted in increased extinction of bacterial populations. We demonstrate that extinction is favored by low rates of spontaneous resistance emergence and low levels of spontaneous cross-resistance among the antibiotics in sequence. The uncovered principles may help to guide the optimized use of available antibiotics in highly potent, evolution-informed treatment designs."}],"pmid":1,"publication_status":"published","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publication":"eLife","date_published":"2021-07-28T00:00:00Z","article_number":"e68876"}]