{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T17:47:51Z","timestamp":1758044871956,"version":"3.44.0"},"reference-count":45,"publisher":"Microbiology Society","issue":"9","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014718","name":"Innovative Research Group Project of the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["No. 82372301"],"award-info":[{"award-number":["No. 82372301"]}],"id":[{"id":"10.13039\/100014718","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Science and Technology Program of Guangzhou","award":["No. 2025A04J4119"],"award-info":[{"award-number":["No. 2025A04J4119"]}]},{"name":"Science and Technology Program of Guangzhou","award":["No. 2025A03J3844"],"award-info":[{"award-number":["No. 2025A03J3844"]}]},{"name":"President Foundation of Nanfang Hospital, Southern Medical University","award":["No. 2023A016"],"award-info":[{"award-number":["No. 2023A016"]}]},{"DOI":"10.13039\/501100003785","name":"Medical Scientific Research Foundation of Guangdong Province of China","doi-asserted-by":"crossref","award":["No. A2024348"],"award-info":[{"award-number":["No. A2024348"]}],"id":[{"id":"10.13039\/501100003785","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,12]]},"abstract":"<jats:p>\n                  <jats:bold>Introduction.<\/jats:bold> Azoles are extensively employed as clinical antifungal agents; however, their long-term and widespread application contributed to the progressive emergence of azole resistance. A significant increase in infections caused by azole-resistant <jats:italic>Nakaseomyces glabrata<\/jats:italic> highlights the need for novel therapeutic strategies.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Hypothesis\/Gap Statement.<\/jats:bold> The efficacy of hexyl-aminolevulinate ethosome-mediated antimicrobial photodynamic therapy (HAL-ES-aPDT) against drug-resistant fungal pathogens, as well as its underlying mechanisms, remains to be elucidated. Our previous studies have demonstrated that HAL-ES-aPDT, which utilizes the photosensitizer HAL-ES, eliminates pathogens via photochemical reactions.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Aim.<\/jats:bold> This study aimed to evaluate the effects and mechanisms of HAL-ES-aPDT on clinical isolates of <jats:italic>N. glabrata<\/jats:italic> exhibiting varying levels of azole susceptibility, with a focus on changes in resistance and virulence.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methodology.<\/jats:bold> Several clinical isolates of <jats:italic>N. glabrata<\/jats:italic> were collected, and the effects and mechanisms of HAL-ES-aPDT treatment on azole-resistant strains were investigated.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results.<\/jats:bold> HAL-ES-aPDT reduced <jats:italic>N. glabrata<\/jats:italic> tolerance to environmental stress and reversed azole resistance by inhibiting drug efflux and downregulating genes encoding the target enzymes. It also attenuated <jats:italic>in vivo<\/jats:italic> virulence by downregulating the expression of the epithelial adhesin gene <jats:italic>EPA1<\/jats:italic>.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusion.<\/jats:bold> These results confirm the efficacy of HAL-ES-aPDT against azole-resistant <jats:italic>N. glabrata<\/jats:italic> and provide novel mechanistic insights that may facilitate the development of effective therapeutic interventions for resistant fungal infections.<\/jats:p>","DOI":"10.1099\/jmm.0.002060","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T16:16:35Z","timestamp":1757693795000},"source":"Crossref","is-referenced-by-count":0,"title":["Role and mechanism of hexyl-aminolevulinate ethosome-mediated antimicrobial photodynamic therapy in reversing fluconazole resistance in Nakaseomyces glabrata (Candida 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