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Loss-of-function mutations in the quorum-sensing regulatory gene\n                      <jats:italic toggle=\"yes\">lasR<\/jats:italic>\n                      commonly arise during chronic infections, which are associated with exaggerated inflammation and accelerated decline in lung function. Here, in a murine cutaneous abscess model, infection with a \u0394\n                      <jats:italic toggle=\"yes\">lasR<\/jats:italic>\n                      mutant or a wild-type-\u0394\n                      <jats:italic toggle=\"yes\">lasR<\/jats:italic>\n                      mutant-mixed population resulted in higher bacterial loads and more severe tissue damage than infection by the wild-type strain. The Rhl and PQS quorum-sensing system genes, as well as phospholipase genes, were upregulated in the \u0394\n                      <jats:italic toggle=\"yes\">lasR<\/jats:italic>\n                      mutant and the wild-type-\u0394\n                      <jats:italic toggle=\"yes\">lasR<\/jats:italic>\n                      mutant-mixed population, which is mediated by PhoB in response to the\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      low-phosphate environments. We further demonstrate an auto-regulatory mechanism of PhoB and identify two LasR-regulated small RNAs that directly repress the translation of\n                      <jats:italic toggle=\"yes\">phoB<\/jats:italic>\n                      . Overall, our results reveal a novel regulatory mechanism whereby mutation of\n                      <jats:italic toggle=\"yes\">lasR<\/jats:italic>\n                      increases the pathogenesis of\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      , providing an explanation for the more severe course of infection with the appearance of\n                      <jats:italic toggle=\"yes\">lasR<\/jats:italic>\n                      -defective mutants.\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 an opportunistic pathogen that causes life-threatening infections. The bacterial quorum-sensing systems play important roles in coordinating gene expression during infection. Loss-of-function mutations in a quorum-sensing regulator gene\n                      <jats:italic toggle=\"yes\">lasR<\/jats:italic>\n                      are commonly found in clinical isolates, which are associated with more rapid lung function decline. Here, in a murine cutaneous abscess model, we demonstrate that the presence of a\n                      <jats:italic toggle=\"yes\">lasR<\/jats:italic>\n                      -defective mutant results in hyperproduction of virulence factors, increased antibiotic resistance, and more severe tissue damage, which resembles the human circumstance. We further identify the host environment signal and a novel regulatory pathway whereby mutation of\n                      <jats:italic toggle=\"yes\">lasR<\/jats:italic>\n                      increases the bacterial pathogenesis. Our findings offer new insights into the LasR-mediated regulatory network in response to the host environment and provide clues to understand the lung disease progression driven by\n                      <jats:italic toggle=\"yes\">lasR<\/jats:italic>\n                      -defective mutants.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01788-25","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T13:01:26Z","timestamp":1756990886000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["<i>Pseudomonas aeruginosa lasR<\/i>\n                    -deficient mutant contributes to bacterial virulence through enhancing the PhoB-mediated pathway in response to host 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