{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:33:19Z","timestamp":1753882399485,"version":"3.41.2"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100019690","name":"Medical Research Council Centre for Medical Mycology","doi-asserted-by":"publisher","award":["MR\/N006364\/2, MR\/V033417\/1"],"award-info":[{"award-number":["MR\/N006364\/2, MR\/V033417\/1"]}],"id":[{"id":"10.13039\/501100019690","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIHR Exeter Biomedical Research Council","award":["NIHR203320"],"award-info":[{"award-number":["NIHR203320"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2025,5,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Broad-spectrum activity is a desirable property of novel antifungal drugs, but relevant\n              <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n              testing is complicated by differential nutritional requirements and growth dynamics of fungal pathogens. Many screens for novel drugs are initiated against individual species or genera, with hit compounds later tested for \u201cpan-fungal\u201d activity. Hypothesizing that an optimized pan-fungal methodology would enhance the efficiency of early-stage drug discovery, a standardized assay was developed for a selection of World Health Organization-defined critical and high-priority fungal pathogens. Instead of using the standard susceptibility testing broth RPMI, an enriched media \u201cfungal RPMI\u201d (fRPMI), including multiple additional fungal growth-enhancing nutrients, was utilized. To assess utility for pan-fungal growth assessments, growth in fRPMI was compared to RPMI medium for 12 fungal pathogens. Growth was significantly improved in 7\/12 species in fRPMI after 24 and\/or 48 hours. For our proof-of-principle study, 500 chemical fragments from the Maybridge Ro3 Fragment library were screened at concentrations of 0.1 or 1 mM against five fungal pathogens:\n              <jats:italic toggle=\"yes\">Aspergillus fumigatus<\/jats:italic>\n              ,\n              <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n              ,\n              <jats:italic toggle=\"yes\">Candida auris<\/jats:italic>\n              ,\n              <jats:italic toggle=\"yes\">Cryptococcus neoformans<\/jats:italic>\n              , and\n              <jats:italic toggle=\"yes\">Nakaseomyces glabratus<\/jats:italic>\n              . Assay quality was assessed using\n              <jats:italic toggle=\"yes\">z<\/jats:italic>\n              -factor analysis, and hits were normalized using a standard\n              <jats:italic toggle=\"yes\">z<\/jats:italic>\n              -score to identify outliers. All assays achieved a high-quality\n              <jats:italic toggle=\"yes\">z<\/jats:italic>\n              -factor (\u22650.5) with readings at \u226424 hours, allowing the identification of 23 compounds with antifungal activity against at least one fungal species. From these, five compounds were identified as having pan-assay interference or broadly toxic properties. In conclusion, hits identified from pan-fungal phenotypic growth-based assays demonstrate reproducibility in all fungal species tested with carefully optimized conditions and precise timing.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01328-24","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T22:48:12Z","timestamp":1743547692000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["A novel pan-fungal screening platform for antifungal drug discovery: proof of principle study"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8128-9990","authenticated-orcid":true,"given":"Rebecca","family":"Inman","sequence":"first","affiliation":[{"name":"Department of Biosciences, Faculty of Health and Life Sciences, Medical Research Council Center for Medical Mycology at the University of Exeter","place":["Exeter, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adilia","family":"Warris","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Faculty of Health and Life Sciences, Medical Research Council Center for Medical Mycology at the University of Exeter","place":["Exeter, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7748-1920","authenticated-orcid":true,"given":"Elaine","family":"Bignell","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Faculty of Health and Life Sciences, Medical Research Council Center for Medical Mycology at the University of Exeter","place":["Exeter, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/mmy\/myz012"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/ph14121312"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof3040057"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.00142-23"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules15064129"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof9020171"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00720-1"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00472-w"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi3005126"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2020.09.003"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.01392"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof7010009"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.01453"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2023.2208687"},{"key":"e_1_3_3_16_2","volume-title":"EUCAST definitive document E.Def 9.4: method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for conidia forming moulds","author":"European Committee on Antimicrobial Susceptibility Testing","year":"2022","unstructured":"European Committee on Antimicrobial Susceptibility Testing. 2022. EUCAST definitive document E.Def 9.4: method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for conidia forming moulds. ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST)."},{"key":"e_1_3_3_17_2","volume-title":"EUCAST definitive document E.Def 7.3.2 revision: method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for yeasts","author":"European Committee on Antimicrobial Susceptibility Testing","year":"2020","unstructured":"European Committee on Antimicrobial Susceptibility Testing. 2020. EUCAST definitive document E.Def 7.3.2 revision: method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for yeasts. ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST)."},{"key":"e_1_3_3_18_2","series-title":"CLSI Standard M27","volume-title":"Reference method for broth dilution antifungal susceptibility testing of yeasts","author":"CLSI","year":"2017","unstructured":"CLSI. 2017. Reference method for broth dilution antifungal susceptibility testing of yeasts. 4th ed. CLSI Standard M27. Clinical and Laboratory Standards Institute, Wayne, PA.","edition":"4"},{"key":"e_1_3_3_19_2","series-title":"CLSI Standard M38","volume-title":"Reference method for broth dilution antifungal susceptibility testing of filamentous fungi","author":"CLSI","year":"2017","unstructured":"CLSI. 2017. Reference method for broth dilution antifungal susceptibility testing of filamentous fungi. 3rd ed. CLSI Standard M38. Clinical and Laboratory Standards Institute, Wayne, PA.","edition":"3"},{"key":"e_1_3_3_20_2","volume-title":"WHO fungal priority pathogens list to guide research, development and public health action","author":"WHO","year":"2022","unstructured":"WHO. 2022. WHO fungal priority pathogens list to guide research, development and public health action. World Health Organization, Geneva."},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48592-8"},{"key":"e_1_3_3_22_2","unstructured":"van Rhijn N. 2020. A genome scale census of virulence factors in the major mould pathogen of human lungs Aspergillus fumigatus. Student Thesis. Phd University of Manchester. https:\/\/research.manchester.ac.uk\/en\/studentTheses\/a-genome-scale-census-of-virulence-factors-in-the-major-mould-pat."},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/mmy\/myaa075"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.simyco.2018.06.001"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2022.01.028"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00328721"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/mmy\/myz127"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/151.3.979"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004261"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1177\/108705719900400206"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1608304113"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1199"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.111"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.1c00657"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.0c00006"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2013.07.001"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2019.05.004"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.4155\/fmc-2016-0025"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2020.03.005"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00539-21"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.5b00111"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1177\/1087057111433459"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1101\/2024.07.19.602466"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1012105"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1101\/2023.06.17.545405"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00498-23"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyab029"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01611-0"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01328-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.01328-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T13:01:20Z","timestamp":1746622880000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.01328-24"}},"subtitle":[],"editor":[{"given":"Damian J.","family":"Krysan","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,5,7]]},"references-count":47,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5,7]]}},"alternative-id":["10.1128\/aac.01328-24"],"URL":"https:\/\/doi.org\/10.1128\/aac.01328-24","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"type":"print","value":"0066-4804"},{"type":"electronic","value":"1098-6596"}],"subject":[],"published":{"date-parts":[[2025,5,7]]},"assertion":[{"value":"2024-09-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01328-24"}}