{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:08:53Z","timestamp":1787062133450,"version":"build-2736575974"},"reference-count":109,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSystems"],"published-print":{"date-parts":[[2025,8,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Within-host environments are complex and multidimensional, making it challenging to link the evolutionary responses of colonizing pathogens to causal selective drivers. Loss of quorum sensing (QS) via mutation of the master regulator,\n                      <jats:italic toggle=\"yes\">lasR<\/jats:italic>\n                      , is a common adaptation of\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      during chronic infections. Here, we use experimental evolution in host-mimicking media to show that loss of QS is constrained by environmental factors associated with host inflammation. Specifically, environments combining oxidative stress and abundant free amino acids limited loss of QS, whereas QS loss was rapid in the absence of oxidative stress, regardless of amino acids. Under oxidative stress,\n                      <jats:italic toggle=\"yes\">lasR<\/jats:italic>\n                      mutations were contingent upon first decoupling regulation of oxidative stress responses from QS via mutations in the promoter region of the primary catalase,\n                      <jats:italic toggle=\"yes\">katA<\/jats:italic>\n                      , or in the oxidative stress regulator,\n                      <jats:italic toggle=\"yes\">oxyR<\/jats:italic>\n                      , enabling maintenance of oxidative stress tolerance. Together, our findings suggest that host inflammatory responses likely delay the loss of QS while colonizers undergo stepwise evolution, first adapting to survive lethal stressors before responding to other nutritional selective drivers that favor loss of QS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      is a common cause of chronic infections characterized by persistent inflammation. Host inflammatory responses alter within-host environments, including by increasing levels of antimicrobial stressors and releasing free amino acids through proteolysis. Here, we show stepwise adaptation of experimental\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      populations to inflammation-like environments, first adapting to survive lethal stress by decoupling oxidative stress responses from quorum sensing (QS), before then adapting to the nutritional conditions, delaying the loss of quorum sensing. These results highlight the power of using laboratory evolution experiments to disentangle the multidimensional selective forces driving pathogen adaptation in complex within-host environments.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/msystems.01722-24","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T08:00:11Z","timestamp":1751875211000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Inflammation-like environments limit the loss of quorum sensing in\n                    <i>Pseudomonas aeruginosa<\/i>"],"prefix":"10.1128","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4683-2171","authenticated-orcid":false,"given":"Taoran","family":"Fu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/027m9bs27","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester","place":["Manchester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna C. 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