{"date_created":"2025-04-27T22:02:13Z","title":"Pulsatile basal gene expression as a fitness determinant in bacteria","oa_version":"Published Version","OA_place":"publisher","project":[{"grant_number":"CZI01","_id":"c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473","name":"Tools for automation and feedback microscopy"},{"name":"Non-canonical antibiotic interactions","_id":"bd6f94d1-d553-11ed-ba76-ae9f07250f74","grant_number":"E219"},{"_id":"34e076d6-11ca-11ed-8bc3-aec76c41a181","grant_number":"I05127","name":"Evolutionary analysis of gene regulation"}],"citation":{"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>","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.","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>.","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>.","short":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, Proceedings of the National Academy of Sciences 122 (2025).","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.","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>"},"file":[{"relation":"main_file","access_level":"open_access","file_size":2949523,"date_updated":"2025-06-24T07:27:43Z","file_id":"19888","file_name":"2025_PNAS_Jain.pdf","checksum":"115a687f40009660eb4b38b4f6559d41","creator":"dernst","date_created":"2025-06-24T07:27:43Z","content_type":"application/pdf","success":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."}],"department":[{"_id":"CaGu"},{"_id":"Bio"},{"_id":"FyKo"},{"_id":"GaTk"}],"has_accepted_license":"1","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"author":[{"last_name":"Jain","id":"330F0278-F248-11E8-B48F-1D18A9856A87","first_name":"Kirti","full_name":"Jain, Kirti"},{"first_name":"Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","last_name":"Hauschild","full_name":"Hauschild, Robert"},{"full_name":"Bochkareva, Olga","last_name":"Bochkareva","first_name":"Olga","id":"C4558D3C-6102-11E9-A62E-F418E6697425","orcid":"0000-0003-1006-6639"},{"full_name":"Römhild, Roderich","last_name":"Römhild","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","first_name":"Roderich","orcid":"0000-0001-9480-5261"},{"last_name":"Tkačik","first_name":"Gašper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper"},{"last_name":"Guet","orcid":"0000-0001-6220-2052","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"}],"intvolume":"       122","article_processing_charge":"Yes (in subscription journal)","issue":"15","pmid":1,"ddc":["570"],"article_number":"e2413709122","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.","acknowledged_ssus":[{"_id":"Bio"}],"publication":"Proceedings of the National Academy of Sciences","year":"2025","oa":1,"date_published":"2025-04-15T00:00:00Z","file_date_updated":"2025-06-24T07:27:43Z","license":"https://creativecommons.org/licenses/by/4.0/","type":"journal_article","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"OA_type":"hybrid","day":"15","related_material":{"record":[{"id":"19294","status":"public","relation":"research_data"}]},"scopus_import":"1","external_id":{"pmid":["40193613"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","doi":"10.1073/pnas.2413709122","article_type":"original","volume":122,"publication_status":"published","corr_author":"1","month":"04","quality_controlled":"1","publisher":"National Academy of Sciences","_id":"19626","date_updated":"2025-06-24T07:28:08Z","status":"public","language":[{"iso":"eng"}]}