{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:10:28Z","timestamp":1785409828380,"version":"3.56.0"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100020916","name":"E\u00f6tv\u00f6s Lor\u00e1nd Research Network","doi-asserted-by":"crossref","award":["HUN-REN 2001007"],"award-info":[{"award-number":["HUN-REN 2001007"]}],"id":[{"id":"10.13039\/100020916","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011019","name":"Nemzeti Kutat\u00e1si Fejleszt\u00e9si \u00e9s Innov\u00e1ci\u00f3s Hivatal","doi-asserted-by":"crossref","award":["TKP2021-EGA-28"],"award-info":[{"award-number":["TKP2021-EGA-28"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Betulinic acid (BA), in combined application with amphotericin B, shows a synergistic effect against\n                      <jats:italic toggle=\"yes\">Candida<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Aspergillus<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Scedosporium<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Fusarium<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">Mucorales<\/jats:italic>\n                      fungi at a concentration as low as 0.125 \u00b5g\/mL. Amphotericin B showed slightly higher affinity towards BA than toward ergosterol, according to our\n                      <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                      molecular docking results, explaining the observed Eagle effect. Moreover, it can bind both molecules simultaneously, suggesting the possibility of the formation of mixed pores, thus increasing the membrane-disrupting activity.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The rising incidence of invasive fungal infections, coupled with the emergence of antifungal resistance, presents a significant challenge in clinical settings. The inherent resistance of certain fungi to conventional antifungal agents, alongside the limitations posed by side effects and drug interactions, necessitates the exploration of alternative therapeutic strategies. This study highlights the potential of combining amphotericin B (AmB) with betulinic acid (BA) to enhance antifungal efficacy against clinically relevant pathogens, including\n                        <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">Aspergillus fumigatus<\/jats:italic>\n                        , as well as mucormycosis-causing fungi. The results demonstrate the synergistic interactions between AmB and BA, which effectively inhibited fungal growth at lower concentrations and are within reported serum levels.\n                        <jats:italic toggle=\"yes\">In silico<\/jats:italic>\n                        molecular docking studies further support the hypothesis that BA may facilitate AmB\u2019s mechanism of action, potentially leading to increased pore formation in fungal membranes.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03333-24","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T09:00:51Z","timestamp":1747386051000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Synergistic interaction of amphotericin B and betulinic acid against clinically important fungi: evidence from\n                    <i>in vitro<\/i>\n                    and\n                    <i>in silico<\/i>\n                    techniques"],"prefix":"10.1128","volume":"13","author":[{"given":"Bence","family":"Rafael","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01pnej532","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biotechnology and Microbiology, Faculty of Science and Informatics, University of Szeged","place":["Szeged, Hungary"]},{"id":[{"id":"https:\/\/ror.org\/01pnej532","id-type":"ROR","asserted-by":"publisher"}],"name":"HUN-REN-SZTE Fungal Pathomechanisms Research Group, University of Szeged","place":["Szeged, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nika","family":"Homa","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01pnej532","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biotechnology and Microbiology, Faculty of Science and Informatics, University of Szeged","place":["Szeged, 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