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U.S.A."],"published-print":{"date-parts":[[2026,6,2]]},"abstract":"<jats:p>\n                    Bacteria often proliferate within confined spaces imposed by host tissues, extracellular matrices, or their own biofilms where cells press against surrounding materials and experience elevated mechanical stress. Whether these forces influence pathogen physiology and fitness remains unresolved. We show that\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                    <\/jats:italic>\n                    adapts to mechanical confinement by increasing resilience to antibiotics. Using synthetic hydrogels of tunable stiffness that restrict expansion without limiting nutrient access, we demonstrate that growth in elastic materials reduces\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                    <\/jats:italic>\n                    sensitivity to antibiotics in a stiffness-dependent manner. Although slower growth contributes to tolerance, Tn-seq under colistin and tobramycin treatment identified key regulators of mechanically induced tolerance. We found that active efflux mediated by sodium\u2013proton\n                    <jats:italic toggle=\"yes\">Sha<\/jats:italic>\n                    antiporters, together with protective remodeling of the bacterial membrane, enhances the resilience of confined populations without impacting growth. These findings reveal that\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                    <\/jats:italic>\n                    adapts to mechanical stress in ways that may promote treatment failure even in the absence of intrinsic resistance.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2605176123","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T17:39:58Z","timestamp":1780076398000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":3,"title":["Growth in confinement promotes\n                    <i>Pseudomonas aeruginosa<\/i>\n                    tolerance to antibiotics"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1938-3717","authenticated-orcid":false,"given":"Sourabh","family":"Monnappa","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02s376052","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Bioengineering and Global Health Institute, School of Life Sciences, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne","place":["Lausanne, Switzerland"]},{"id":[{"id":"https:\/\/ror.org\/02s376052","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Mechanical Engineering and Bioengineering, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne","place":["Lausanne, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zainebe","family":"Al-Mayyah","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02s376052","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Bioengineering and Global Health Institute, School of Life Sciences, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne","place":["Lausanne, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7226-3382","authenticated-orcid":false,"given":"Mahmut Selman","family":"Sakar","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02s376052","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Mechanical Engineering and Bioengineering, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne","place":["Lausanne, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8426-8255","authenticated-orcid":false,"given":"Alexandre","family":"Persat","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02s376052","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Bioengineering and Global Health Institute, School of Life Sciences, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne","place":["Lausanne, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-019-0314-2"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.005"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2016.12.002"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.227694"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/mmbr.00094-20"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2016.01.005"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1502025112"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.02671"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2101759118"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1222981"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2415"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703218104"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.03.042"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.01.012"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43827-6"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2015.10.004"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2018.05.006"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2107107118"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.4c05503"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202206153"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.56533"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06552-z"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","unstructured":"L. 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