{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T16:08:35Z","timestamp":1789834115011,"version":"4.0.1"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"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":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,12,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The escalating spread of multidrug-resistant (MDR) Gram-negative pathogens, particularly\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Acinetobacter baumannii<\/jats:italic>\n                      , has severely undermined the efficacy of polymyxin B, one of the few remaining last-line antibiotics. Here, we identify hyperforin, a natural product derived from\n                      <jats:italic toggle=\"yes\">Hypericum perforatum<\/jats:italic>\n                      , as a potent polymyxin B adjuvant capable of restoring its antibacterial activity against clinical Gram-negative isolates with high-level polymyxin resistance. Using a suite of\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      assays, including fractional inhibitory concentration index, time-kill kinetics, biofilm eradication, membrane integrity assays, and ultrastructural imaging of the bacterial outer membrane, we show that hyperforin significantly enhances polymyxin B-mediated bacterial killing. Microscopy and\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      -phenyl-1-naphthylamine uptake are consistent with membrane perturbation, and increased intracellular reactive oxygen species is consistent with oxidative stress under combination treatment. Taken together, these orthogonal readouts support a working model of complementary membrane perturbation and oxidative stress. Remarkably, the observed synergistic effects occur at concentrations potentially achievable in the epithelial lining fluid of the lungs, providing a testable rationale for localized lung delivery (e.g., via a dry-powder inhaler). These findings unveil a promising therapeutic strategy that repurposes a bioactive phytochemical to potentiate polymyxins against otherwise untreatable polymyxin-resistant MDR Gram-negative infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01007-25","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T14:08:26Z","timestamp":1762956506000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Hyperforin potentiates polymyxin B against multidrug-resistant Gram-negative pathogens via membrane disruption, biofilm eradication, and oxidative stress"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5922-7312","authenticated-orcid":true,"given":"Maytham","family":"Hussein","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bfwt286","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacology, Monash Biomedicine Discovery Institute, Monash University","place":["Clayton, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Crawford","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bfwt286","id-type":"ROR","asserted-by":"publisher"}],"name":"Ramaciotti Centre for Cryo-EM, Monash Biomedicine Discovery Institute, Monash University","place":["Clayton, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Baker","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00eae9z71","id-type":"ROR","asserted-by":"publisher"}],"name":"Discipline of Biological Sciences, Priority Research Centre in Reproductive Biology, Faculty of Science and IT, University of Newcastle, University Drive","place":["Callaghan, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Floyd","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Molecular Biosciences, The University of Queensland","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafah","family":"Allobawi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bfwt286","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacology, Monash Biomedicine Discovery Institute, Monash University","place":["Clayton, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9447-2292","authenticated-orcid":true,"given":"Mark A. T.","family":"Blaskovich","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Superbug Solutions and ARC Training Centre for Environmental and Agricultural Solutions to Antimicrobial Resistance, Institute for Molecular Bioscience, The University of Queensland","place":["Saint Lucia, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8704-7770","authenticated-orcid":true,"given":"Gauri G.","family":"Rao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Titus Family Department of Clinical Pharmacy, University of Southern California","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Zuegg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Molecular Biosciences, The University of Queensland","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7953-8230","authenticated-orcid":true,"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bfwt286","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Monash Biomedicine Discovery Institute, Monash University","place":["Clayton, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0017-7952","authenticated-orcid":false,"given":"Tony","family":"Velkov","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bfwt286","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacology, Monash Biomedicine Discovery Institute, Monash University","place":["Clayton, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12668-019-00658-4"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01867-1"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30753-3"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens11121420"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14040786"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-78769-6"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a025288"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(06)70580-1"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm900999h"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00834-10"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1201\/b10787-12"},{"key":"e_1_3_3_13_2","volume-title":"The greek herbal of dioscordes","author":"Gunther R","year":"1968","unstructured":"Gunther R. 1968. 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