{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T04:49:34Z","timestamp":1783745374338,"version":"3.55.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"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":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,12,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality globally, often exacerbated by infections such as methicillin-resistant\n              <jats:italic>Staphylococcus aureus<\/jats:italic>\n              (MRSA). The rise in antibiotic-resistant strains complicates treatment and underscores the need for novel therapeutic drugs. In this paper, we further investigated the antimicrobial potential of a fluoropyrimidine anticancer drug doxifluridine against multidrug-resistant\n              <jats:italic>S. aureus<\/jats:italic>\n              . Determination of minimum inhibitory concentration (MIC) or minimum bactericidal concentration (MBC), monitoring of growth curve, time-kill assays, biofilm bactericidal assays, and chequerboard studies were conducted to evaluate the antibacterial efficacy of doxifluridine. Safety was assessed via hemolysis and cytotoxicity assays, and an\n              <jats:italic>in vivo Galleria mellonella<\/jats:italic>\n              larvae model was employed to test protective effects. Doxifluridine demonstrated significant antibacterial activity against clinical multidrug resistance (MDR)\n              <jats:italic>S. aureus<\/jats:italic>\n              isolates, with MIC and MBC values ranging from 0.5 to 2 \u00b5g\/mL and 1 to 4 \u00b5g\/mL, respectively. The results revealed doxifluridine\u2019s potent bactericidal effects within 8 hours. Moreover, doxifluridine-treated bacteria showed a substantial reduction in biofilm mass and viability. Furthermore, chequerboard assays indicated synergistic interactions between doxifluridine and other antibiotics, reducing MIC values by two- to eightfold. More importantly, safety evaluations confirmed that doxifluridine did not exhibit hemolytic toxicity or cytotoxicity. Finally, doxifluridine significantly increased the survival rate of MRSA-infected\n              <jats:italic>G. mellonella<\/jats:italic>\n              larvae\n              <jats:italic>in vivo<\/jats:italic>\n              . In brief, doxifluridine exhibited promising\n              <jats:italic>in vitro<\/jats:italic>\n              and\n              <jats:italic>in vivo<\/jats:italic>\n              antibacterial activity against MRSA, suggesting its potential as a repurposed drug for treating resistant bacterial infections in COPD patients.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                The study provides robust evidence for the antibacterial efficacy of doxifluridine against Methicillin-resistant\n                <jats:italic>Staphylococcus aureus<\/jats:italic>\n                in chronic obstructive pulmonary disease (COPD) patients. Its rapid action, ability to disrupt biofilms, and synergistic effects with other antibiotics, combined with a favorable safety profile, highlight its potential as a repurposed therapeutic agent. Future clinical trials will be essential to confirm these findings and pave the way for its integration into clinical practice. This work not only provides candidate for tackling the management of bacterial infections in COPD but also exemplifies the potential of drug repurposing in combating antibiotic-resistant infections.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.01805-24","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T14:01:08Z","timestamp":1731420068000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Doxifluridine effectively kills antibiotic-resistant\n            <i>Staphylococcus aureus<\/i>\n            in chronic obstructive pulmonary disease"],"prefix":"10.1128","volume":"12","author":[{"given":"Lianshen","family":"Zhang","sequence":"first","affiliation":[{"name":"Respiratory and Critical Care Medicine Department, Tongxiang Second People\u2019s Hospital","place":["Tongxiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Respiratory and Critical Care Medicine Department, Tongxiang Second People\u2019s Hospital","place":["Tongxiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Tian","sequence":"additional","affiliation":[{"name":"General Clinic, Chongfu Town Community Health Service Center","place":["Tongxiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Shen","sequence":"additional","affiliation":[{"name":"Respiratory and Critical Care Medicine Department, Tongxiang Second People\u2019s Hospital","place":["Tongxiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9516-9523","authenticated-orcid":false,"given":"Xiaolong","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Respiratory, The Affiliated Hospital of Jiaxing University","place":["Jiaxing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.03.00063703"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.76"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.20452\/pamw.1134"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000639"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201503-126AW"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005837"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000142"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2200"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.168"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00041"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1468"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4306"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2013.256"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-0282-0"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.9b00745"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612823666170209154745"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1995.13.10.2613"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1177\/030089169307900510"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-004-0983-y"},{"key":"e_1_3_4_22_2","volume-title":"Performance standards for antimicrobial susceptibility testing","author":"Clinical and Laboratory Standards Institute","year":"2007","unstructured":"Clinical and Laboratory Standards Institute. 2007. 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