{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:15:13Z","timestamp":1788581713752,"version":"build-2803163510"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province","award":["2022E10022"],"award-info":[{"award-number":["2022E10022"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,6,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      ) is the primary pathogenic bacterium causing nosocomial-acquired infections, particularly in immunocompromised individuals. Owing to the abuse of colistin (COL), a frontline drug in clinical settings, the resistance rate of\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      to COL has been escalating year by year, exerting a severe impact on public health. To solve this clinical problem, new therapeutic approaches are urgently required. This study initially proposes a strategy of using carvone in combination with COL to combat colistin-resistant\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      (COL-R\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      ). The checkerboard assay and time-kill assay validated the\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      antibacterial action of this combination against COL-R\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      . Furthermore, crystalline violet staining and scanning electron microscopy (SEM) confirmed that the combined treatment effectively inhibited biofilm formation. Moreover, the thigh infection model in neutropenic mice showcased the\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      effectiveness of the combined therapy. In addition, the erythrocyte hemolysis experiment and the\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      safety assessment revealed that the combination of carvone and COL exhibited a certain level of safety at effective concentrations. The synergistic antibacterial and antibiofilm mechanisms of carvone combined with COL may be associated with the inhibition of quorum-sensing gene expression, enhancement of bacterial inner and outer membrane permeability, and increased generation of reactive oxygen species. This study offered a new therapeutic strategy for COL-R\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      infections.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The increasing prevalence of colistin-resistant\n                        <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                        (COL-R\n                        <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                        ) poses a significant threat to global public health, as it limits treatment options for severe infections. This study investigates the synergistic effects of carvone, a natural compound, combined with colistin (COL) to combat COL-R\n                        <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                        both in\n                        <jats:italic toggle=\"yes\">vitro<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                        . The findings reveal that carvone can restore the susceptibility of COL-R\n                        <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                        to COL. By exploring this novel combination, the research aims to provide a potential alternative therapeutic strategy for COL-R\n                        <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                        infections. The findings could pave the way for new approaches to treat infections caused by this resilient pathogen.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02307-25","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T13:00:07Z","timestamp":1778763607000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of the combined efficacy of carvone and colistin against colistin-resistant\n                    <i>Pseudomonas aeruginosa<\/i>\n                    :\n                    <i>in vitro<\/i>\n                    and\n                    <i>in vivo<\/i>\n                    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