{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:45:18Z","timestamp":1785415518497,"version":"3.56.0"},"reference-count":63,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2021YFD1800405"],"award-info":[{"award-number":["2021YFD1800405"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32373066"],"award-info":[{"award-number":["32373066"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007847","name":"Natural Science Foundation of Jilin Province","doi-asserted-by":"publisher","award":["20230101142JC"],"award-info":[{"award-number":["20230101142JC"]}],"id":[{"id":"10.13039\/100007847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Colistin is considered one of the last-resort antibiotics for treating infections caused by multidrug-resistant (MDR) Gram-negative bacteria. However, the emergence and dissemination of mobile colistin resistance gene,\n                      <jats:italic toggle=\"yes\">mcr<\/jats:italic>\n                      , have severely compromised the clinical utility of colistin. Combination therapy has emerged as a promising strategy to restore and enhance antibiotic efficacy against such bacterial infections. In this study, we identified broxyquinoline (BRO), an antiprotozoal compound, as a potent colistin adjuvant that significantly enhanced colistin activity against both colistin-susceptible and colistin-resistant Gram-negative bacteria by markedly reducing the minimum inhibitory concentration. Mechanistically, BRO disrupts bacterial membrane integrity, increases membrane permeability and fluidity, collapses the proton motive force, induces reactive oxygen species (ROS) accumulation, and depletes intracellular ATP, collectively disturbing bacterial homeostasis. Additionally, BRO exhibited high-affinity binding to lipopolysaccharide (LPS) and attenuated subsequent LPS-induced inflammatory responses in host cells. In murine thigh and lung infection models, the BRO-colistin combination restored colistin efficacy\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      , evidenced by significantly reduced bacterial loads. In the lung infection model, this combination further improved survival, alleviated pulmonary pathological damage, and reduced the levels of pro-inflammatory cytokines (TNF-\u03b1, IL-1\u03b2) in bronchoalveolar lavage fluid. Collectively, these findings support the BRO-colistin combination as a promising therapeutic strategy to overcome colistin resistance and combat MDR Gram-negative infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01398-25","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T14:00:21Z","timestamp":1770127221000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Broxyquinoline enhances antibacterial activity of colistin and attenuates LPS-induced inflammation"],"prefix":"10.1128","volume":"70","author":[{"given":"Rui","family":"Ding","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00js3aw79","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases & Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University","place":["Changchun, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelong","family":"Ma","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00js3aw79","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases & Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University","place":["Changchun, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyao","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00js3aw79","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases & Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University","place":["Changchun, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayang","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00js3aw79","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases & Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University","place":["Changchun, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonglin","family":"Zhou","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00js3aw79","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases & Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University","place":["Changchun, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00js3aw79","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases & Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University","place":["Changchun, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtao","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00js3aw79","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases & Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University","place":["Changchun, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6411-1074","authenticated-orcid":true,"given":"Xuming","family":"Deng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00js3aw79","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases & Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University","place":["Changchun, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7723-5073","authenticated-orcid":true,"given":"Jiazhang","family":"Qiu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00js3aw79","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases & Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University","place":["Changchun, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4171-4453","authenticated-orcid":false,"given":"Shizhen","family":"Ma","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00js3aw79","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases & Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University","place":["Changchun, People's Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.281.1.61"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.352.6287.758"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/595011"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(10)70258-9"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00424-7"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1586\/eri.12.78"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2013.03.012"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.15190\/d.2019.15"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.11.5.852"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.10.012"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.559"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abb3791"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2119417119"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.45951"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00348"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01326"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1004"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109772"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01376-23"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1699-0463.1978.tb00025.x"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr516"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adk6331"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.2c00205"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02753081"},{"key":"e_1_3_4_26_2","first-page":"505","article-title":"Therapeutic trial of a combination of broxyquinoline and brobenzoxaldine in the treatment of leprosy","volume":"51","author":"Hazra SK","year":"1979","unstructured":"Hazra SK, Ghosh S, Kundu SK, Chaudhuri S. 1979. Therapeutic trial of a combination of broxyquinoline and brobenzoxaldine in the treatment of leprosy. Lepr India 51:505\u2013510.","journal-title":"Lepr India"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2019.03.004"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-0877-5"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00901-13"},{"key":"e_1_3_4_30_2","volume-title":"Performance standards for antimicrobial disk and dilution susceptibility tests for bacteria isolated from animals","author":"Michael T. Sweeney M","year":"2024","unstructured":"Michael T. Sweeney M. 2024. Performance standards for antimicrobial disk and dilution susceptibility tests for bacteria isolated from animals. 6th ed. Clinical and Laboratory Standards Institute.","edition":"6"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201703383"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/jam.13702"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2024.2353492"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03899-4"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2011.11.057"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.106.095711"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.11.026"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02346-19"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-020-0723-z"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.2c06615"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.65836"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2020.09.008"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1080\/1040841X.2018.1492902"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/med.21946"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202304397"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0669-6"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.71.110601.135414"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1179\/096805106X118825"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/448645a"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202100681"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-024-01807-6"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02854-z"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S49763"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1021\/la504407v"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.4c01574"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00182-24"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.99130"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11060716"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2007036117"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1159\/000496370"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002051"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.96678"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-015-1865-4"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01398-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01398-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T14:01:08Z","timestamp":1772632868000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01398-25"}},"subtitle":[],"editor":[{"given":"Vincent H.","family":"Tam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":63,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3,4]]}},"alternative-id":["10.1128\/aac.01398-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.01398-25","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,4]]},"assertion":[{"value":"2025-09-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01398-25"}}