{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T07:02:24Z","timestamp":1775890944299,"version":"3.50.1"},"posted":{"date-parts":[[2025,2,3]]},"group-title":"Microbiology","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T00:00:00Z","timestamp":1738540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,2,3]]},"abstract":"<jats:title>\n                  <jats:bold>ABSTRACT<\/jats:bold>\n                <\/jats:title>\n                <jats:p>\n                  We investigated the activity of the tuberculosis drug SQ109 against sixteen fungal pathogens:\n                  <jats:italic>Candida albicans<\/jats:italic>\n                  ,\n                  <jats:italic>C. auris<\/jats:italic>\n                  ,\n                  <jats:italic>C. glabrata<\/jats:italic>\n                  ,\n                  <jats:italic>C. guilliermondi<\/jats:italic>\n                  ,\n                  <jats:italic>C. kefyr<\/jats:italic>\n                  ,\n                  <jats:italic>C. krusei<\/jats:italic>\n                  ,\n                  <jats:italic>C. lusitaniae<\/jats:italic>\n                  ,\n                  <jats:italic>Candida parapsilosis<\/jats:italic>\n                  ,\n                  <jats:italic>C. tropicalis, Cryptococcus neoformans<\/jats:italic>\n                  ,\n                  <jats:italic>Rhizopus<\/jats:italic>\n                  spp.,\n                  <jats:italic>Mucor<\/jats:italic>\n                  spp.,\n                  <jats:italic>Fusarium<\/jats:italic>\n                  spp.,\n                  <jats:italic>Coccidioides<\/jats:italic>\n                  spp.,\n                  <jats:italic>Histoplasma capsulatum<\/jats:italic>\n                  and\n                  <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                  . MIC values varied widely (125 ng\/mL to &gt;64 \u00b5g\/mL) but in many cases we found promising (MIC\u223c4 \u00b5g\/mL) activity as well as MFC\/MIC ratios of \u223c2. SQ109 metabolites were inactive. The activity of 12 analogs of SQ109 against\n                  <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                  correlated with protonophore uncoupling activity, suggesting mitochondrial targeting, consistent with the observation that growth inhibition was rescued by agents which inhibit ROS species accumulation. SQ109 disrupted H\n                  <jats:sup>+<\/jats:sup>\n                  \/Ca\n                  <jats:sup>2+<\/jats:sup>\n                  homeostasis in\n                  <jats:italic>S. cerevisiae<\/jats:italic>\n                  vacuoles, and there was synergy (FICI\u223c0.31) with pitavastatin, indicating involvement of isoprenoid biosynthesis pathway inhibition. SQ109 is, therefore, a potential antifungal agent with multi-target activity.\n                <\/jats:p>","DOI":"10.1101\/2025.02.03.636131","type":"posted-content","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T22:20:20Z","timestamp":1738621220000},"source":"Crossref","is-referenced-by-count":0,"title":["Broad-Spectrum Activity and Mechanisms of Action of SQ109 on a Variety of Fungi"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7606-1932","authenticated-orcid":false,"given":"Satish R.","family":"Malwal","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rocio","family":"Garcia-Rubio","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, United 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