article Pulsatile basal gene expression as a fitness determinant in bacteria published yes Kirti Jain author 330F0278-F248-11E8-B48F-1D18A9856A870000-0002-3809-0449 Robert Hauschild author 4E01D6B4-F248-11E8-B48F-1D18A9856A870000-0001-9843-3522 Olga Bochkareva author C4558D3C-6102-11E9-A62E-F418E66974250000-0003-1006-6639 Roderich Römhild author 68E56E44-62B0-11EA-B963-444F3DDC885E0000-0001-9480-5261 Gašper Tkačik author 3D494DCA-F248-11E8-B48F-1D18A9856A870000-0002-6699-1455 Calin C Guet author 47F8433E-F248-11E8-B48F-1D18A9856A870000-0001-6220-2052 CaGu department Bio department FyKo department GaTk department Tools for automation and feedback microscopy project Non-canonical antibiotic interactions project Evolutionary analysis of gene regulation project 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. https://research-explorer.ista.ac.at/download/19626/19888/2025_PNAS_Jain.pdf application/pdfno https://creativecommons.org/licenses/by/4.0/ National Academy of Sciences2025 eng Proceedings of the National Academy of Sciences 0027-8424 1091-6490 40193613 00147123520000110.1073/pnas.2413709122 12215 https://research-explorer.ista.ac.at/record/19294 https://ista.ac.at/en/news/clockwork-just-for-antibiotic-resistance/ K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, Proceedings of the National Academy of Sciences 122 (2025). 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> 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. 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>. 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>. 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> 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. 196262025-04-27T22:02:13Z2026-04-28T13:35:46Z