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A key determinant of\n              <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n              virulence is the regulated synthesis and release of extracellular products, which is controlled by a cell density-dependent signaling system known as quorum sensing (QS).\n              <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n              uses a complex QS network, including two systems that rely on diffusible N-acylhomoserine lactone (AHL) signal molecules. The LuxR-type receptor RhlR is unique in that it requires not only its cognate AHL but also the accessory protein PqsE to maximally bind to promoter DNA and initiate transcription. Our group previously demonstrated that PqsE physically interacts with RhlR, enhancing its affinity for target promoters across the\n              <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n              genome. Although LuxR-type receptors are widespread in Gram-negative bacteria and important for pathogenesis, PqsE orthologs are restricted to\n              <jats:italic toggle=\"yes\">Pseudomonas<\/jats:italic>\n              and\n              <jats:italic toggle=\"yes\">Burkholderia<\/jats:italic>\n              species. This study explored the conservation of PqsE and examined PqsE ortholog structure-function across different species. Our results show that PqsE in\n              <jats:italic toggle=\"yes\">Pseudomonas<\/jats:italic>\n              retains their functional interactions with RhlR homologs, unlike PqsE orthologs in\n              <jats:italic toggle=\"yes\">Burkholderia<\/jats:italic>\n              spp., which do not interact with their respective LuxR-type receptors. Additionally, we assessed the AHL preferences of different receptors and hypothesized that the PqsE-RhlR interaction evolved to stabilize the inherently unstable RhlR, preventing its degradation. Indeed, we observe higher levels of RhlR protein turnover in a strain lacking\n              <jats:italic toggle=\"yes\">pqsE<\/jats:italic>\n              compared to a wild-type strain of PA14, which can be partially rescued in a strain of\n              <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n              lacking the Lon protease.\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              , a major pathogen for patients with cystic fibrosis and a primary constituent of healthcare-associated infections, relies on a complex quorum-sensing (QS) network to coordinate virulence factor production. Central to this system is the interaction between two proteins, PqsE and RhlR, which drive gene expression essential for pathogenesis. Our study investigates the conservation of the PqsE-RhlR interaction across related bacterial species, revealing that PqsE in\n              <jats:italic toggle=\"yes\">Pseudomonas<\/jats:italic>\n              can enhance RhlR activity, while orthologs in\n              <jats:italic toggle=\"yes\">Burkholderia<\/jats:italic>\n              lack this capacity. These findings offer new insights into the specificity and evolution of QS mechanisms, highlighting the PqsE-RhlR interaction as a potentially selective target for treating\n              <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n              infections.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.00646-25","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T13:14:10Z","timestamp":1744118050000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Evolution of PqsE as a\n            <i>Pseudomonas aeruginosa<\/i>\n            -specific regulator of LuxR-type receptors: insights from\n            <i>Pseudomonas<\/i>\n            and\n            <i>Burkholderia<\/i>"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1114-513X","authenticated-orcid":true,"given":"Caleb 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