{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:08:34Z","timestamp":1791644914303,"version":"4.3.4"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Ministry for Culture and Innovation, Hungary","award":["EK\u00d6P-24-0"],"award-info":[{"award-number":["EK\u00d6P-24-0"]}]},{"name":"Ministry for Culture and Innovation, Hungary","award":["EK\u00d6P-25-4-II-DE-59"],"award-info":[{"award-number":["EK\u00d6P-25-4-II-DE-59"]}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["J\u00e1nos Bolyai Research Scholarschip"],"award-info":[{"award-number":["J\u00e1nos Bolyai Research Scholarschip"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hungarian National Research, Development and Innovation Office","award":["FK138462"],"award-info":[{"award-number":["FK138462"]}]},{"name":"Hungarian National Research, Development and Innovation Office","award":["Starting 150834"],"award-info":[{"award-number":["Starting 150834"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Candida<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">Candidozyma<\/jats:italic>\n                      )\n                      <jats:italic toggle=\"yes\">auris<\/jats:italic>\n                      is an emerging multidrug-resistant fungal pathogen capable of establishing persistent skin colonization, contaminating the environment, and causing nosocomial outbreaks associated with high mortality rates. Conventional monotherapy frequently proves inadequate against biofilm-associated infections, underscoring the urgent need for novel therapeutic strategies. Therefore, we investigated the physiological and molecular responses of South Asian clade\n                      <jats:italic toggle=\"yes\">C. auris<\/jats:italic>\n                      biofilms to treatment with a caspofungin\u2013posaconazole combination. This regimen markedly reduced the median minimum inhibitory concentrations (4- to 32-fold for caspofungin; 8- to 64-fold for posaconazole) compared with monotherapies. Synergistic interactions were observed in all isolates, with fractional inhibitory concentration indices ranging from 0.078 to 0.31, and were further confirmed\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . Transcriptomic profiling revealed activation of multiple stress-response pathways, driving adaptive changes such as enhanced extracellular matrix production and biofilm-forming capacity, maintenance of intracellular cation homeostasis, osmotic stress response, and extensive cell wall and membrane remodeling affecting the mannan\u2013glucan complex, chitin, sphingolipids, phosphatidylinositol-(4,5)-bisphosphate, and ergosterol content. Additional responses included activation of\n                      <jats:italic toggle=\"yes\">RCT1<\/jats:italic>\n                      (fluconazole-inducible protein) and\n                      <jats:italic toggle=\"yes\">MDR1<\/jats:italic>\n                      (drug efflux pump), collectively promoting survival under combined antifungal pressure. These findings demonstrate the potent synergistic activity of caspofungin and posaconazole against\n                      <jats:italic toggle=\"yes\">C. auris<\/jats:italic>\n                      biofilms, thereby supporting the development of effective combination therapies for this high-risk pathogen.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Candida auris<\/jats:italic>\n                        is a rapidly emerging fungal pathogen that presents substantial challenges for infection control owing to its multidrug resistance, persistence in healthcare environments, and capacity to cause large-scale outbreaks. Biofilm formation on indwelling medical devices plays a pivotal role in\n                        <jats:italic toggle=\"yes\">C. auris<\/jats:italic>\n                        outbreaks within healthcare settings and is implicated in nearly 90% of\n                        <jats:italic toggle=\"yes\">C. auris<\/jats:italic>\n                        candidemia cases. These biofilms also exhibit pronounced tolerance to antifungal agents, thereby restricting available treatment options. Our study demonstrates that the combination of caspofungin and posaconazole exerts a strong synergistic effect against\n                        <jats:italic toggle=\"yes\">C. auris<\/jats:italic>\n                        biofilms, both\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                        . By elucidating the molecular mechanisms behind this synergy\u2014including stress-response activation, cell wall and membrane remodeling, calcium signaling, and regulation of drug efflux pumps\u2014this work provides important insights into antifungal therapeutic responses in\n                        <jats:italic toggle=\"yes\">C. auris<\/jats:italic>\n                        and underscores combination therapy as a promising strategy to overcome biofilm-associated antifungal resistance in this high-risk pathogen.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02686-25","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T13:01:14Z","timestamp":1773320474000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Synergistic activity of caspofungin and posaconazole against\n                    <i>Candida<\/i>\n                    (\n                    <i>Candidozyma<\/i>\n                    )\n                    <i>auris<\/i>\n                    biofilms based on phenotypic, transcriptomic, and\n                    <i>in vivo<\/i>\n                    insights"],"prefix":"10.1128","volume":"14","author":[{"given":"Fruzsina","family":"Kov\u00e1cs","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, University of Debrecen","place":["Debrecen, Hungary"]},{"id":[{"id":"https:\/\/ror.org\/02xf66n48","id-type":"ROR","asserted-by":"publisher"}],"name":"Doctoral School of Pharmaceutical Sciences, University of Debrecen","place":["Debrecen, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Harmath","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, University of Debrecen","place":["Debrecen, Hungary"]},{"id":[{"id":"https:\/\/ror.org\/02xf66n48","id-type":"ROR","asserted-by":"publisher"}],"name":"Doctoral School of Pharmaceutical Sciences, University of Debrecen","place":["Debrecen, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e1vid","family":"Bal\u00e1zsi","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, University of Debrecen","place":["Debrecen, Hungary"]},{"id":[{"id":"https:\/\/ror.org\/02xf66n48","id-type":"ROR","asserted-by":"publisher"}],"name":"Doctoral School of Pharmaceutical Sciences, University of Debrecen","place":["Debrecen, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lajos","family":"Forg\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, University of Debrecen","place":["Debrecen, 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