{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:07:41Z","timestamp":1782281261480,"version":"3.54.5"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Invasive fungal infections and emerging antifungal resistance threaten global public health, demanding effective combination therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To evaluate\n                      <jats:italic>in vitro<\/jats:italic>\n                      synergistic antifungal activity of betulinic acid (BA) combined with four azoles (itraconazole [ITR], voriconazole [VOR], posaconazole [POS], fluconazole [FLC]) against\n                      <jats:italic>Aspergillus<\/jats:italic>\n                      spp.,\n                      <jats:italic>Candida<\/jats:italic>\n                      spp.,\n                      <jats:italic>Exophiala dermatitidis<\/jats:italic>\n                      , and\n                      <jats:italic>Cryptococcus neoformans<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Per CLSI M27\u2013A3\/M38\u2013A2, broth microdilution checkerboard assay determined BA\u2019s minimum inhibitory concentration (MIC) and synergy with azoles (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f110); flow cytometry measured intracellular reactive oxygen species (ROS) in fungi co\u2013cultured with BA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BA alone had no antifungal activity, but showed synergy with specific azoles: BA\/POS had 82.7% (43\/52) synergy against\n                      <jats:italic>Aspergillus<\/jats:italic>\n                      spp., 95.2% (20\/21) against\n                      <jats:italic>E. dermatitidis<\/jats:italic>\n                      , and 70% (7\/10) against\n                      <jats:italic>Candida auris<\/jats:italic>\n                      (of 28\n                      <jats:italic>Candida<\/jats:italic>\n                      spp., 28.6% synergy). BA\/FLC had 55.6% (5\/9) synergy against\n                      <jats:italic>C. neoformans<\/jats:italic>\n                      . Among the 110 strains, the synergy rates of BA with POS, ITR and VOR were 66.4, 10.9 and 2.7%, respectively; the BA\u2013FLC synergy rate was 18.5% in 27 strains. BA\/POS co\u2013culture increased fungal ROS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      BA\u2013POS reduces POS\u2019s MIC and exerts potent synergy against\n                      <jats:italic>Aspergillus<\/jats:italic>\n                      spp. and\n                      <jats:italic>E. dermatitidis.<\/jats:italic>\n                      BA has potential as an adjuvant for treating\n                      <jats:italic>Aspergillus<\/jats:italic>\n                      and\n                      <jats:italic>E. dermatitidis<\/jats:italic>\n                      infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1835794","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:45:27Z","timestamp":1782279927000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["In vitro synergistic activity of betulinic acid combined with azoles against pathogenic fungi"],"prefix":"10.3389","volume":"17","author":[{"given":"Heng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Dermatology, Hubei Provincial Clinical Research Center for Diagnosis and Therapeutics of Pathogenic Fungal Infection, Jingzhou Hospital Affiliated to Yangtze University","place":["Jingzhou, Hubei Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Yangtze University","place":["Jingzhou, Hubei Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqi","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Yangtze University","place":["Jingzhou, Hubei Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghua","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Yangtze University","place":["Jingzhou, Hubei Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Yangtze University","place":["Jingzhou, Hubei Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmiao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Jingzhou Hospital Affiliated to Yangtze University, Hubei Provincial Clinical Research Center for Diagnosis and Therapeutics of Pathogenic Fungal Infection","place":["Jingzhou, Hubei Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hubei Provincial Clinical Research Center for Diagnosis and Therapeutics of Pathogenic Fungal Infection, Jingzhou Hospital Affiliated to Yangtze University","place":["Jingzhou, Hubei Province, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s41182-024-00628-x","article-title":"In vitro antifungal activities of medicinal plants used for treatment of candidiasis in Pader district, northern Uganda","volume":"52","author":"Akwongo","year":"2024","journal-title":"TROP MED HEALTH"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"439","DOI":"10.3389\/fmicb.2012.00439","article-title":"Ergosterol biosynthesis in Aspergillus fumigatus: its relevance as an antifungal target and role in antifungal drug resistance","volume":"3","author":"Alcazar-Fuoli","year":"2013","journal-title":"Front. 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