{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T02:16:54Z","timestamp":1784081814215,"version":"3.55.0"},"reference-count":28,"publisher":"Microbiology Society","issue":"11","funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"crossref","award":["67\/2\/2020-DDI\/BMS"],"award-info":[{"award-number":["67\/2\/2020-DDI\/BMS"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"crossref"}]},{"name":"SERB Early Career Research Award","award":["ECR\/2016\/000102"],"award-info":[{"award-number":["ECR\/2016\/000102"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,22]]},"abstract":"<jats:p>\n                  <jats:bold>Introduction.<\/jats:bold> Mucormycosis is an aggressive, angioinvasive infection associated with high morbidity and mortality. The disease remains difficult to treat, with limited available antifungal drugs. Consequently, there is an urgent need to develop alternate therapeutics against mucormycosis. In an earlier study, we demonstrated that the non-steroidal anti-inflammatory drug diflunisal impacted the actin cytoskeleton and quorum sensing and inhibited the formation of filopodia-\/cytoneme-like extensions in <jats:italic>Rhizopus arrhizus<\/jats:italic>.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Hypothesis.<\/jats:bold> The non-steroidal anti-inflammatory drug diflunisal could exhibit potential antifungal activity.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Aim.<\/jats:bold> This study aimed to investigate the plausible antifungal activity of diflunisal against a range of medically important <jats:italic>Mucorales<\/jats:italic> and its combination effect with antifungal drugs.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methodology.<\/jats:bold> The antifungal activity of diflunisal against <jats:italic>Rhizopus arrhizus, Lichtheimia corymbifera, Rhizomucor pusillus<\/jats:italic>, <jats:italic>Cunninghamella bertholletiae<\/jats:italic>, <jats:italic>Mucor indicus, Mucor irregularis<\/jats:italic> and <jats:italic>Apophysomyces elegans<\/jats:italic> was evaluated by broth microdilution assay. Allied salicylates were also screened. A combination assay with amphotericin B deoxycholate and posaconazole was performed by fractional inhibitory concentration test.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results.<\/jats:bold> Exposure to diflunisal inhibited <jats:italic>Rhizopus arrhizus<\/jats:italic> spore germination in a dose-dependent manner. MICs of diflunisal against different <jats:italic>Mucorales<\/jats:italic> ranged from 64 to 2048 \u00b5g ml<jats:sup>\u22121<\/jats:sup>. Remarkably low levels of diflunisal (0.03\u20132 \u00b5g ml<jats:sup>\u22121<\/jats:sup>), depending on the strain\/species tested, improved the antifungal activity of amphotericin B against mucoralean fungi by twofold (\u03a3FIC \u2248 0.5\u20130.508; <jats:italic>P&lt;<\/jats:italic>0.01). Field-emission scanning electron micrographs further confirmed these observations. MICs of posaconazole were unchanged by this compound.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusion.<\/jats:bold> Considering that amphotericin B remains the first-line drug against mucormycosis and exhibits dose-dependent side effects in clinical practice, especially nephrotoxicity, the observed additive interaction at remarkably low, clinically achievable levels of diflunisal demonstrates its potential utility as an adjunct therapy against mucoralean fungi.<\/jats:p>","DOI":"10.1099\/jmm.0.001929","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T15:15:30Z","timestamp":1732288530000},"source":"Crossref","is-referenced-by-count":2,"title":["Repurposing the non-steroidal anti-inflammatory drug diflunisal as an adjunct therapy with amphotericin B against mucoralean fungi"],"prefix":"10.1099","volume":"73","author":[{"given":"Anjna","family":"Kumari","sequence":"first","affiliation":[{"name":"Department of Microbial Biotechnology, Panjab University, Chandigarh 160014, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasdeep","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Microbial Biotechnology, Panjab University, Chandigarh 160014, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pallavi","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Microbial Biotechnology, Panjab University, Chandigarh 160014, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahaldeep","family":"Kaur","sequence":"additional","affiliation":[{"name":"Present address: Laboratory of Clinical Immunology and Microbiology, Epithelial Therapeutics Unit, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA"},{"name":"Department of Microbial Biotechnology, Panjab University, Chandigarh 160014, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9041-0251","authenticated-orcid":false,"given":"Rachna","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Microbial Biotechnology, Panjab University, Chandigarh 160014, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-022-01172-2"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1111\/myc.12243"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1111\/myc.13335"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30312-3"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01244-19"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1093\/femsec\/fiaa170"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1007\/s00248-021-01765-0"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.008243"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2014.04.005"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1111\/1567-1364.12119"},{"key":"R11","first-page":"950","volume-title":"CLSI Standard M38 (ISBN 1-56238-830-4 [Print]; 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