{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:26:42Z","timestamp":1768505202281,"version":"3.49.0"},"posted":{"date-parts":[[2023,1,20]]},"group-title":"Microbiology","reference-count":25,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,1,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  New antifungal therapies are needed for both systemic, invasive infections as well as superficial infections of mucosal and skin surfaces as well as biofilms associated with medical devices. The resistance of biofilm and biofilm-like growth phases of fungi contributes to the poor efficacy of systemic therapies to non-systemic infections. Here, we describe the identification and characterization of a novel keto-alkyl-pyridinium scaffold with broad spectrum activity (2-16 \u00b5g\/mL) against medically important yeasts and moulds, including clinical isolates resistant to azoles and\/or echinocandins. Furthermore, these keto-alkyl-pyridinium agents retain substantial activity against biofilm phase yeast and have direct activity against hyphal\n                  <jats:italic>A. fumigatus<\/jats:italic>\n                  . Although their toxicity precludes use in systemic infections, we found that the keto-alkyl-pyridinium molecules reduce\n                  <jats:italic>C. albicans<\/jats:italic>\n                  fungal burden in a rat model of vascular catheter infection and reduce\n                  <jats:italic>Candida auris<\/jats:italic>\n                  colonization in a porcine ex vivo model. These initial pre-clinical data suggest that molecules of this class may warrant further study and development.\n                <\/jats:p>","DOI":"10.1101\/2023.01.19.524835","type":"posted-content","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T22:50:21Z","timestamp":1674255021000},"source":"Crossref","is-referenced-by-count":0,"title":["Novel keto-alkyl-pyridinium antifungal molecules active in models of in vivo\n                  <i>Candida albicans<\/i>\n                  vascular catheter infection and ex vivo\n                  <i>Candida auris<\/i>\n                  skin colonization"],"prefix":"10.64898","author":[{"given":"Sarah R.","family":"Beattie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taiwo","family":"Esan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Zarnowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Eix","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8587-6244","authenticated-orcid":false,"given":"Jeniel E.","family":"Nett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7927-9950","authenticated-orcid":false,"given":"David R.","family":"Andes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Hagen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6330-3365","authenticated-orcid":false,"given":"Damian J.","family":"Krysan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023012403550912000_2023.01.19.524835v1.1","first-page":"857","volume-title":"J Fungi","volume":"8","year":"2022"},{"key":"2023012403550912000_2023.01.19.524835v1.2","doi-asserted-by":"crossref","first-page":"881272","DOI":"10.3389\/fcimb.2022.881272","article-title":"Editorial: Antifungal Pipeline: build it strong; build it better","volume":"12","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"2023012403550912000_2023.01.19.524835v1.3","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.13.101"},{"key":"2023012403550912000_2023.01.19.524835v1.4","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00458-19"},{"key":"2023012403550912000_2023.01.19.524835v1.5","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ933"},{"key":"2023012403550912000_2023.01.19.524835v1.6","doi-asserted-by":"publisher","DOI":"10.1086\/599376"},{"key":"2023012403550912000_2023.01.19.524835v1.7","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s40588-020-00143-7","article-title":"Candida auris infection and biofilm formation: going beyond the surface","volume":"7","year":"2020","journal-title":"Curr Clin Microbiol Rep"},{"key":"2023012403550912000_2023.01.19.524835v1.8","doi-asserted-by":"crossref","first-page":"804","DOI":"10.3390\/jof7100804","article-title":"Augmenting the activity of chlorhexidine for decolonization of Candida auris from porcine skin","volume":"7","year":"2021","journal-title":"J Fungi"},{"key":"2023012403550912000_2023.01.19.524835v1.9","doi-asserted-by":"crossref","first-page":"102208","DOI":"10.1016\/j.mib.2022.102208","article-title":"The molecular and genetic basis of antifungal resistance in the emerging fungal pathogen Candida auris","volume":"70","year":"2022","journal-title":"Curr Opin Microbiol"},{"key":"2023012403550912000_2023.01.19.524835v1.10","doi-asserted-by":"crossref","first-page":"e0005322","DOI":"10.1128\/aac.00053-22","article-title":"Candida auris pan-drug-resistant to four classes of antifungal agents","volume":"66","year":"2022","journal-title":"Antimicrob Agents Chemother"},{"key":"2023012403550912000_2023.01.19.524835v1.11","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00231-10"},{"key":"2023012403550912000_2023.01.19.524835v1.12","doi-asserted-by":"crossref","unstructured":"Shen M , Li PT , Wu YJ , Lin CH , Chai E , Chang TC , Chen CT. The antifungal activities and biological consequences of BMVC-12C-P, a carbazole derivative against Candida species. Med Mycol. 58:521\u2013529.","DOI":"10.1093\/mmy\/myz071"},{"key":"2023012403550912000_2023.01.19.524835v1.13","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.2.843-845.2005"},{"key":"2023012403550912000_2023.01.19.524835v1.14","doi-asserted-by":"crossref","first-page":"e0010022","DOI":"10.1128\/spectrum.00100-22","article-title":"Disruption of iron homeostasis and mitochondrial metabolism are promising targets to inhibit Candida auris","volume":"10","year":"2022","journal-title":"Microbiol Spectr"},{"key":"2023012403550912000_2023.01.19.524835v1.15","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1002\/cmdc.201800331","article-title":"Synthesis and evaluation of a series of bis(pentylpyridinium) compounds as antifungal agents","volume":"13","year":"2018","journal-title":"ChemMedChem"},{"issue":"4","key":"2023012403550912000_2023.01.19.524835v1.16","doi-asserted-by":"crossref","first-page":"e0053921","DOI":"10.1128\/mSphere.00539-21","article-title":"A unique dual-readout high throughput screening assay to identify antifungal compounds with Aspergillus fumigatus","volume":"6","year":"2021","journal-title":"mSphere"},{"key":"2023012403550912000_2023.01.19.524835v1.17","first-page":"e00576","article-title":"Ceylpyridinium chloride: mechanism of action, antimicrobial efficacy in biofilms, and potential risks of resistance","volume":"64","year":"2020","journal-title":"Antimicrob Agents Chemother"},{"key":"2023012403550912000_2023.01.19.524835v1.18","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.7.1482"},{"key":"2023012403550912000_2023.01.19.524835v1.19","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.9.2475-2479.2001"},{"key":"2023012403550912000_2023.01.19.524835v1.20","doi-asserted-by":"crossref","first-page":"ofab444","DOI":"10.1093\/ofid\/ofab444","article-title":"Antifungal susceptibility testing: a primer for clinicians","volume":"8","year":"2021","journal-title":"Open Forum Infect Dis"},{"key":"2023012403550912000_2023.01.19.524835v1.21","first-page":"1067","volume-title":"J Fungi","volume":"8","year":"2022"},{"key":"2023012403550912000_2023.01.19.524835v1.22","first-page":"e00722","article-title":"In vitro and in vivo activity of a novel catheter lock solution against bacterial and fungal biofilms","volume":"62","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"2023012403550912000_2023.01.19.524835v1.23","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-539-8_40"},{"key":"2023012403550912000_2023.01.19.524835v1.24","doi-asserted-by":"crossref","unstructured":"Johnson CJ , Cheong JZA , Shanmuganayagam D , Kalan LR , Nett JE. Modeling Candida auris colonization on porcine skin ex-vivo. Methods Mol Biol. 2517:251\u2013258.","DOI":"10.1007\/978-1-0716-2417-3_20"},{"key":"2023012403550912000_2023.01.19.524835v1.25","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.chom.2020.12.002","article-title":"Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors, and therapeutic strategies","volume":"29","year":"2021","journal-title":"ell Host Microbe"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.01.19.524835","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:10:02Z","timestamp":1768450202000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.01.19.524835"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,20]]},"references-count":25,"URL":"https:\/\/doi.org\/10.1101\/2023.01.19.524835","relation":{},"subject":[],"published":{"date-parts":[[2023,1,20]]},"subtype":"preprint"}}