{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:02:30Z","timestamp":1790744550416,"version":"4.1.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Elizabethkingia<\/jats:italic>\n                      spp. are intrinsically resistant to multiple antimicrobial classes and are emerging nosocomial pathogens. This study evaluated the antibacterial activity of fingolimod against\n                      <jats:italic>Elizabethkingia<\/jats:italic>\n                      and its interaction with minocycline.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Sixteen residual clinical isolates were examined. Baseline single-agent susceptibility was assessed by a single disk-diffusion determination and by VITEK 2. Fingolimod MIC and MBC values were measured by broth microdilution. Biofilm formation was quantified by crystal violet staining. Fingolimod\u2013minocycline interactions were evaluated by checkerboard and time-kill assays. Preliminary protective activity was examined in a\n                      <jats:italic>Galleria mellonella<\/jats:italic>\n                      model infected with EA12.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Disk diffusion and VITEK 2 showed method-dependent discordance for piperacillin\u2013tazobactam. Fifteen of 16 isolates formed biofilm; 13 of these 15 were weak and two were moderate producers. Fingolimod MICs ranged from 6.25 to 25 \u03bcg\/mL. Fingolimod reduced the minocycline MIC by 4\u20138-fold in six synergistic isolates. The combination produced preliminary, isolate-specific protection in\n                      <jats:italic>Galleria mellonella<\/jats:italic>\n                      infected with EA12.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Fingolimod exhibits antibacterial activity against\n                      <jats:italic>Elizabethkingia<\/jats:italic>\n                      spp. and potentiates minocycline in a subset of isolates. These findings support further development of fingolimod-based combination strategies and optimization of the fingolimod scaffold.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1924132","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:50:51Z","timestamp":1790743851000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Fingolimod potentiates minocycline against multidrug-resistant Elizabethkingia"],"prefix":"10.3389","volume":"16","author":[{"given":"Jie","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, The Affiliated Taian City Central Hospital of Qingdao University","place":["Taian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Affiliated Taian City Central Hospital of Qingdao University","place":["Taian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Zong","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Affiliated Taian City Central Hospital of Qingdao University","place":["Taian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongliang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyou","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongpeng","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1007\/s12098-022-04467-8","article-title":"Clinical profile and outcome of neonates with Elizabethkingia sepsis","volume":"90","author":"Anil","year":"2023","journal-title":"Indian J. Pediatr."},{"key":"B2","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1038\/nrd3248","article-title":"Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis","volume":"9","author":"Brinkmann","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"B3","doi-asserted-by":"publisher","first-page":"463","DOI":"10.7883\/yoken.66.463","article-title":"Determination of in vitro activities of polymyxin B and rifampin in combination with ampicillin\/sulbactam or cefoperazone\/sulbactam against multidrug-resistant Acinetobacter baumannii by the E-test and checkerboard methods","volume":"66","author":"Cetin","year":"2013","journal-title":"Japanese J. Infect. Dis."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.01445-17","article-title":"Elizabethkingia anophelis is the dominant Elizabethkingia species found in blood cultures in Singapore","volume":"56","author":"Chew","year":"2018","journal-title":"J. Clin. Microbiol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10040450","article-title":"Comparative analysis of gradient diffusion and disk diffusion with agar dilution for susceptibility testing of Elizabethkingia anophelis","volume":"10","author":"Chiu","year":"2021","journal-title":"Antibiotics (Basel)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1146\/annurev-pharmtox-010818-021358","article-title":"Fingolimod: lessons learned and new opportunities for treating multiple sclerosis and other disorders","volume":"59","author":"Chun","year":"2019","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1080\/21505594.2019.1621649","article-title":"Galleria mellonella as a consolidated in vivo model hosts: new developments in antibacterial strategies and novel drug testing","volume":"10","author":"Cutuli","year":"2019","journal-title":"Virulence"},{"key":"B8","doi-asserted-by":"publisher","first-page":"15","DOI":"10.2165\/11596550-000000000-00000","article-title":"Clinical pharmacokinetics of fingolimod","volume":"51","author":"David","year":"2012","journal-title":"Clin. Pharmacokinet."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00352-23","article-title":"Repurposing high-throughput screening identifies unconventional drugs with antibacterial and antibiofilm activities against Pseudomonas aeruginosa under experimental conditions relevant to cystic fibrosis","volume":"11","author":"Di Bonaventura","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25031397","article-title":"Fingolimod inhibits exopolysaccharide production and regulates relevant genes to eliminate the biofilm of K. pneumoniae","volume":"25","author":"Geng","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8111834","article-title":"Screening of FDA-approved drugs using a 384-well plate-based biofilm platform: the case of fingolimod","volume":"8","author":"Gilbert-Girard","year":"2020","journal-title":"Microorganisms"},{"key":"B12","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1128\/jcm.01637-16","article-title":"Relative prevalence and antimicrobial susceptibility of clinical isolates of Elizabethkingia species based on 16S rRNA gene sequencing","volume":"55","author":"Han","year":"2017","journal-title":"J. Clin. Microbiol."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/srep26045","article-title":"Elizabethkingia anophelis bacteremia is associated with clinically significant infections and high mortality","volume":"6","author":"Lau","year":"2016","journal-title":"Sci. Rep."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms7090295","article-title":"Elizabethkingia infections in humans: from genomics to clinics","volume":"7","author":"Lin","year":"2019","journal-title":"Microorganisms"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2497","DOI":"10.1093\/jac\/dky197","article-title":"Clinical manifestations, molecular characteristics, antimicrobial susceptibility patterns and contributions of target gene mutation to fluoroquinolone resistance in Elizabethkingia anophelis","volume":"73","author":"Lin","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"B16","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s10482-017-0926-3","article-title":"Revisiting the taxonomy of the genus Elizabethkingia using whole-genome sequencing, optical mapping, and MALDI-TOF, along with proposal of three novel Elizabethkingia species: Elizabethkingia bruuniana sp. nov. Elizabethkingia ursingii sp. nov. and Elizabethkingia occulta sp. nov","volume":"111","author":"Nicholson","year":"2018","journal-title":"Antonie van Leeuwenhoek"},{"key":"B17","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1093\/jac\/dkad394","article-title":"Synergy of polymyxin B and minocycline against KPC-3- and OXA-48-producing Klebsiella pneumoniae in dynamic time-kill experiments: agreement with in silico predictions","volume":"79","author":"Olsson","year":"2024","journal-title":"J. Antimicrob. Chemother."},{"key":"B18","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1186\/s12866-025-03973-x","article-title":"Fingolimod as a potent anti-Staphylococcus aureus: pH-dependent cell envelope damage and eradication of biofilms\/persisters","volume":"25","author":"Shang","year":"2025","journal-title":"BMC Microbiol."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2026.1815762","article-title":"Genomic characterization of respiratory Elizabethkingia: antimicrobial resistance and strain relatedness","volume":"17","author":"Shang","year":"2026","journal-title":"Front. Microbiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S0167-7012(00)00122-6","article-title":"A modified microtiter-plate test for quantification of staphylococcal biofilm formation","volume":"40","author":"Stepanovic","year":"2000","journal-title":"J. Microbiol. Methods"},{"key":"B21","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1080\/21505594.2015.1135289","article-title":"Galleria mellonella infection models for the study of bacterial diseases and for antimicrobial drug testing","volume":"7","author":"Tsai","year":"2016","journal-title":"Virulence"},{"key":"B22","doi-asserted-by":"publisher","first-page":"18465","DOI":"10.1021\/acsomega.1c02591","article-title":"Synthesis and biological evaluation of fingolimod derivatives as antibacterial agents","volume":"6","author":"Zore","year":"2021","journal-title":"ACS Omega"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1924132\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:50:54Z","timestamp":1790743854000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1924132\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":22,"alternative-id":["10.3389\/fcimb.2026.1924132"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1924132","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]},"article-number":"1924132"}}