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These fungi cause severe or chronic mycoses and are typically treated with azoles or amphotericin B. Ambruticin, a polyketide antifungal, shows promise as an alternative therapy. It targets hybrid histidine kinases (HHKs), which are fungal-specific proteins essential for osmoregulation and parasitic morphology and are conserved across thermal dimorphic species. Targeting HHKs suggests that ambruticin may therapeutically treat infections from multiple fungi without causing mechanism-based toxicity. We explore ambruticin\u2019s potential to effectively treat these fungal infections without major adverse effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01225-25","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T14:00:52Z","timestamp":1770213652000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Hybrid histidine kinases and antifungal warfare in thermal dimorphic fungi"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8793-2509","authenticated-orcid":false,"given":"Frances S.","family":"Faguy","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0272j5188","id-type":"ROR","asserted-by":"publisher"}],"name":"Pathogen and Microbiome Institute, Northern Arizona University","place":["Flagstaff, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Walczak","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02ttsq026","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, University of Colorado","place":["Boulder, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3439-4517","authenticated-orcid":false,"given":"Bridget M.","family":"Barker","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0272j5188","id-type":"ROR","asserted-by":"publisher"}],"name":"Pathogen and Microbiome Institute, Northern Arizona University","place":["Flagstaff, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.210219"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2007.04.002"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124105"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2011.07878.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2012.1193"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-13-121"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsyr\/fow047"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.8005"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","unstructured":"Kirkland TN. 2018. 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