{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T05:24:30Z","timestamp":1740720270107,"version":"3.38.0"},"reference-count":44,"publisher":"Portland Press Ltd.","issue":"02","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002642","name":"Korea University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002642","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,2,28]]},"abstract":"<jats:p>The antifungal drugs of the echinocandin family show high efficacy against Aspergillus fumigatus. However, their paradoxical effect, which restores fungal growth at high drug concentrations, and the emergence of resistant strains necessitate improvements. We identified 13 fluoroquinolone compounds from a chemical library containing 10,000 compounds that potentiate the antifungal activity of caspofungin. Among them, NE-E07 significantly enhanced the efficacy of echinocandins against A. fumigatus, including resistant strains, without potentiating other antifungal families like voriconazole or amphotericin B. Specifically, NE-E07 demonstrated a unique ability to potentiate caspofungin\u2019s activity against the echinocandin-resistant strain USHM-M0051 isolated from patients. Our experiments revealed that NE-E07, in combination with caspofungin, affected ergosterol biosynthesis in a manner consistent with azole drugs. Docking tests suggest that NE-E07 has a high binding affinity with CYP51, which affects ergosterol biosynthesis similarly to azole drugs. Interestingly, known fluoroquinolones like ciprofloxacin, nalidixic acid, and norfloxacin did not show this potentiating effect, suggesting that NE-E07\u2019s unique structure is critical for its activity. Moreover, NE-E07 did not enhance echinocandin activity against Candida albicans or Cryptococcus neoformans, highlighting its specific action against A. fumigatus. In vivo studies demonstrated that co-treatment with NE-E07 and caspofungin increased the survival rate of mice infected with A. fumigatus. This significant improvement in survival underscores the potential clinical relevance of NE-E07 as a co-administered drug with echinocandins for treating fungal infections, particularly those resistant to echinocandins.<\/jats:p>","DOI":"10.1042\/bsr20250001","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T14:21:13Z","timestamp":1737382873000},"page":"101-116","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The fluoroquinolone compounds potentiate the antifungal activity of the echinocandins against <i>Aspergillus fumigatus<\/i>"],"prefix":"10.1042","volume":"45","author":[{"given":"Jin-Ju","family":"Choi","sequence":"first","affiliation":[{"name":"1School of Life Sciences and Biotechnology, Korea University, Anam-dong, Sungbuk-gu, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzie","family":"Kang","sequence":"additional","affiliation":[{"name":"1School of Life Sciences and Biotechnology, Korea University, Anam-dong, Sungbuk-gu, Seoul, Republic of Korea"},{"name":"2EsgelBio Co, Anam-dong, Sungbuk-gu, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoonseo","family":"Lee","sequence":"additional","affiliation":[{"name":"1School of Life Sciences and Biotechnology, Korea University, Anam-dong, Sungbuk-gu, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"1School of Life Sciences and Biotechnology, Korea University, Anam-dong, Sungbuk-gu, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuju","family":"Jang","sequence":"additional","affiliation":[{"name":"3Department of Plant Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ja-Il","family":"Goo","sequence":"additional","affiliation":[{"name":"1School of Life Sciences and Biotechnology, Korea University, Anam-dong, Sungbuk-gu, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongseok","family":"Choi","sequence":"additional","affiliation":[{"name":"1School of Life Sciences and Biotechnology, Korea University, Anam-dong, Sungbuk-gu, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongho","family":"Lee","sequence":"additional","affiliation":[{"name":"3Department of Plant Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0697-4768","authenticated-orcid":false,"given":"Cheol-Won","family":"Yun","sequence":"additional","affiliation":[{"name":"1School of Life Sciences and Biotechnology, Korea University, Anam-dong, Sungbuk-gu, Seoul, Republic of Korea"},{"name":"2EsgelBio Co, Anam-dong, Sungbuk-gu, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"2025022710372767300_BSR-2025-0001C1","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s15010-018-1152-2","article-title":"Neuroinfections caused by fungi","volume":"46","author":"G\u00f3ralska","year":"2018","journal-title":"Infection"},{"key":"2025022710372767300_BSR-2025-0001C2","doi-asserted-by":"crossref","DOI":"10.1016\/j.smim.2023.101728","article-title":"Immunity to fungi in the lung","volume":"66","author":"Heung","year":"2023","journal-title":"Semin. Immunol."},{"author":"Zabel","first-page":"55","key":"2025022710372767300_BSR-2025-0001C3"},{"key":"2025022710372767300_BSR-2025-0001C4","doi-asserted-by":"crossref","first-page":"227","DOI":"10.2515\/therapie:2006039","article-title":"Emerging azole antifungals","volume":"61","author":"Wolff","year":"2006","journal-title":"Therapie"},{"key":"2025022710372767300_BSR-2025-0001C5","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3389\/fcell.2016.00057","article-title":"Recognition of membrane sterols by polyene antifungals amphotericin B and natamycin, A (13)C MAS NMR study","volume":"4","author":"Ciesielski","year":"2016","journal-title":"Front. Cell Dev. Biol."},{"key":"2025022710372767300_BSR-2025-0001C6","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/S0140-6736(03)14472-8","article-title":"Echinocandin antifungal drugs","volume":"362","author":"Denning","year":"2003","journal-title":"Lancet"},{"key":"2025022710372767300_BSR-2025-0001C7","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1126\/science.aap7999","article-title":"Worldwide emergence of resistance to antifungal drugs challenges human health and food security","volume":"360","author":"Fisher","year":"2018","journal-title":"Science"},{"key":"2025022710372767300_BSR-2025-0001C8","doi-asserted-by":"crossref","first-page":"5420","DOI":"10.1128\/AAC.00905-16","article-title":"Aspergillus fumigatus intrinsic fluconazole resistance Is due to the naturally occurring T301I substitution in Cyp51Ap","volume":"60","author":"Leonardelli","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"2025022710372767300_BSR-2025-0001C9","doi-asserted-by":"crossref","first-page":"3239","DOI":"10.1128\/AAC.00019-12","article-title":"Impact of prior inappropriate fluconazole dosing on isolation of fluconazole-nonsusceptible Candida species in hospitalized patients with candidemia","volume":"56","author":"Shah","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"2025022710372767300_BSR-2025-0001C10","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1007\/s10096-014-2096-9","article-title":"Emergence of echinocandin-resistant Candida spp. in a hospital setting: A consequence of 10 years of increasing use of antifungal therapy?","volume":"33","author":"Fekkar","year":"2014","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"2025022710372767300_BSR-2025-0001C11","doi-asserted-by":"crossref","DOI":"10.1093\/femsec\/fiz187","article-title":"Antibiotic-induced gut metabolome and microbiome alterations increase the susceptibility to Candida albicans colonization in the gastrointestinal tract","volume":"96","author":"Gutierrez","year":"2020","journal-title":"FEMS Microbiol. Ecol."},{"key":"2025022710372767300_BSR-2025-0001C12","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/iub.1973","article-title":"Synergistic antifungal activity of isoquercitrin: apoptosis and membrane permeabilization related to reactive oxygen species in candida albicans","volume":"71","author":"Kim","year":"2019","journal-title":"IUBMB Life"},{"key":"2025022710372767300_BSR-2025-0001C13","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1080\/1061186X.2020.1803333","article-title":"Coadministration of liposomal methylglyoxal increases the activity of amphotericin B against Candida albicans in leukopoenic mice","volume":"29","author":"Khan","year":"2021","journal-title":"J. Drug Target."},{"key":"2025022710372767300_BSR-2025-0001C14","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1056\/NEJMoa1110404","article-title":"Combination antifungal therapy for cryptococcal meningitis","volume":"368","author":"Day","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"2025022710372767300_BSR-2025-0001C15","doi-asserted-by":"crossref","DOI":"10.1016\/j.envpol.2022.120440","article-title":"Fluoroquinolone antibiotics: Occurrence, mode of action, resistance, environmental detection, and remediation - a comprehensive review","volume":"315","author":"Bhatt","year":"2022","journal-title":"Environ. Pollut."},{"key":"2025022710372767300_BSR-2025-0001C16","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/S1369-5274(99)00008-9","article-title":"Mechanism of fluoroquinolone action","volume":"2","author":"Drlica","year":"1999","journal-title":"Curr. Opin. Microbiol."},{"key":"2025022710372767300_BSR-2025-0001C17","doi-asserted-by":"crossref","DOI":"10.1002\/ardp.201800382","article-title":"Quinolone derivatives and their antifungal activities: An overview","volume":"352","author":"Zhang","year":"2019","journal-title":"Arch. Pharm. (Weinheim)"},{"key":"2025022710372767300_BSR-2025-0001C18","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1080\/14756366.2022.2050224","article-title":"Echinocandins - structure, mechanism of action and use in antifungal therapy","volume":"37","author":"Szyma\u0144ski","year":"2022","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"2025022710372767300_BSR-2025-0001C19","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/S0140-6736(02)11203-7","article-title":"Clinical importance of the cytochromes P450","volume":"360","author":"Nebert","year":"2002","journal-title":"Lancet"},{"key":"2025022710372767300_BSR-2025-0001C20","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/2047-783X-16-4-159","article-title":"Pharmacology and metabolism of anidulafungin, caspofungin and micafungin in the treatment of invasive candidosis: Review of the literature","volume":"16","author":"Kofla","year":"2011","journal-title":"Eur. J. Med. Res."},{"key":"2025022710372767300_BSR-2025-0001C21","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s15010-017-1042-z","article-title":"Pharmacokinetics of antifungal drugs: Practical implications for optimized treatment of patients","volume":"45","author":"Bellmann","year":"2017","journal-title":"Infection"},{"key":"2025022710372767300_BSR-2025-0001C22","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.drup.2007.04.002","article-title":"Resistance to echinocandin-class antifungal drugs","volume":"10","author":"Perlin","year":"2007","journal-title":"Drug Resist. Updat."},{"key":"2025022710372767300_BSR-2025-0001C23","doi-asserted-by":"crossref","first-page":"11976","DOI":"10.1038\/s41598-020-68706-8","article-title":"FKS1 mutation associated with decreased echinocandin susceptibility of Aspergillus fumigatus following anidulafungin exposure","volume":"10","author":"E Silva","year":"2020","journal-title":"Sci. Rep."},{"key":"2025022710372767300_BSR-2025-0001C24","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.00447-22","article-title":"The caspofungin paradoxical effect is a tolerant \u201cEagle Effect\u201d in the filamentous fungal pathogen Aspergillus fumigatus","volume":"13","author":"Valero","year":"2022","journal-title":"mBio"},{"key":"2025022710372767300_BSR-2025-0001C25","doi-asserted-by":"crossref","first-page":"807","DOI":"10.3390\/jof9080807","article-title":"The transcriptome response to azole compounds in Aspergillus fumigatus shows differential gene expression across pathways essential for azole resistance and cell survival","volume":"9","author":"Hokken","year":"2023","journal-title":"J. Fungi (Basel)."},{"key":"2025022710372767300_BSR-2025-0001C26","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1128\/AAC.49.9.3697-3701.2005","article-title":"Efficacy of caspofungin and voriconazole combinations in experimental aspergillosis","volume":"49","author":"MacCallum","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"2025022710372767300_BSR-2025-0001C27","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1086\/513943","article-title":"Invasive Aspergillosis","volume":"26","author":"Denning","year":"1998","journal-title":"Clin. Infect. Dis."},{"key":"2025022710372767300_BSR-2025-0001C28","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S0140-6736(15)01159-9","article-title":"Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial","volume":"387","author":"Maertens","year":"2016","journal-title":"Lancet"},{"key":"2025022710372767300_BSR-2025-0001C29","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1093\/jac\/dkq479","article-title":"Management of invasive fungal infections: A role for polyenes","volume":"66","author":"Chandrasekar","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"2025022710372767300_BSR-2025-0001C30","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1086\/423381","article-title":"Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy","volume":"39","author":"Maertens","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"2025022710372767300_BSR-2025-0001C31","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1080\/14740338.2021.1922667","article-title":"Antifungal agents and the kidney: Pharmacokinetics, clinical nephrotoxicity, and interactions","volume":"20","author":"Tragiannidis","year":"2021","journal-title":"Expert Opin. Drug Saf."},{"key":"2025022710372767300_BSR-2025-0001C32","first-page":"149","article-title":"Clinical hepatotoxicity associated with antifungal agents","volume":"16","author":"Kyriakidis","year":"2017","journal-title":"Expert Opin. Drug Saf."},{"key":"2025022710372767300_BSR-2025-0001C33","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/s41586-023-05856-5","article-title":"Structural and mechanistic insights into fungal \u03b2-1,3-glucan synthase FKS1","volume":"616","author":"Hu","year":"2023","journal-title":"Nature New Biol."},{"key":"2025022710372767300_BSR-2025-0001C34","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s11046-013-9719-z","article-title":"Efficacy of the combination of voriconazole and caspofungin in experimental pulmonary aspergillosis by different Aspergillus species","volume":"177","author":"Zhang","year":"2014","journal-title":"Mycopathologia"},{"key":"2025022710372767300_BSR-2025-0001C35","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1093\/jac\/dkh434","article-title":"Combinations of antifungal agents in therapy--what value are they?","volume":"54","author":"Cuenca-Estrella","year":"2004","journal-title":"J. Antimicrob. Chemother."},{"key":"2025022710372767300_BSR-2025-0001C36","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1097\/01.tp.0000202421.94822.f7","article-title":"Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective, multicenter, observational study","volume":"81","author":"Singh","year":"2006","journal-title":"Transplantation"},{"key":"2025022710372767300_BSR-2025-0001C37","first-page":"373","article-title":"Ciprofloxacin. a review of its antibacterial activity, pharmacokinetic properties and therapeutic use","volume":"35","author":"Campoli-Richards","year":"1988","journal-title":"Drugs (Abingdon Engl)"},{"key":"2025022710372767300_BSR-2025-0001C38","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/phar.2050","article-title":"What is old Is new again: Delafloxacin, a modern fluoroquinolone","volume":"38","author":"Cho","year":"2018","journal-title":"Pharmacotherapy"},{"key":"2025022710372767300_BSR-2025-0001C39","first-page":"677","article-title":"Levofloxacin. a review of its antibacterial activity, pharmacokinetics and therapeutic efficacy","volume":"47","author":"Davis","year":"1994","journal-title":"Drugs (Abingdon Engl)"},{"key":"2025022710372767300_BSR-2025-0001C40","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/0002-9343(87)90612-7","article-title":"Norfloxacin, a fluoroquinolone antibacterial agent. Classification, mechanism of action, and in vitro activity","volume":"82","author":"Goldstein","year":"1987","journal-title":"Am. J. Med."},{"key":"2025022710372767300_BSR-2025-0001C41","doi-asserted-by":"crossref","first-page":"81","DOI":"10.2307\/2480870","article-title":"The nutritional requirements of the fungus, aspergillus niger","volume":"62","author":"Steinberg","year":"1935","journal-title":"Bulletin of the Torrey Botanical Club"},{"key":"2025022710372767300_BSR-2025-0001C42","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1021\/acs.biomac.0c00096","article-title":"Caspofungin functionalized polymethacrylates with antifungal properties","volume":"21","author":"Alex","year":"2020","journal-title":"Biomacromolecules"},{"key":"2025022710372767300_BSR-2025-0001C43","doi-asserted-by":"crossref","first-page":"6728","DOI":"10.1074\/jbc.M117.778308","article-title":"Structural analyses of Candida albicans sterol 14\u03b1-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis","volume":"292","author":"Hargrove","year":"2017","journal-title":"J. Biol. Chem."},{"key":"2025022710372767300_BSR-2025-0001C44","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01919-15","article-title":"The Aspergillus fumigatus damage resistance protein family Coordinately regulates ergosterol biosynthesis and azole susceptibility","volume":"7","author":"Song","year":"2016","journal-title":"mBio"}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/45\/02\/101\/967713\/bsr-2025-0001.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/45\/02\/101\/967713\/bsr-2025-0001.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T10:38:47Z","timestamp":1740652727000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/45\/02\/101\/235561\/The-fluoroquinolone-compounds-potentiate-the"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":44,"journal-issue":{"issue":"02","published-print":{"date-parts":[[2025,2,28]]}},"URL":"https:\/\/doi.org\/10.1042\/bsr20250001","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"type":"print","value":"0144-8463"},{"type":"electronic","value":"1573-4935"}],"subject":[],"published-other":{"date-parts":[[2025,2]]},"published":{"date-parts":[[2025,2]]}}}