{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:51:24Z","timestamp":1786117884064,"version":"build-2736575974"},"reference-count":104,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100011019","name":"Nemzeti Kutat\u00e1si Fejleszt\u00e9si \u00e9s Innov\u00e1ci\u00f3s Hivatal","doi-asserted-by":"crossref","award":["K 146131"],"award-info":[{"award-number":["K 146131"]}],"id":[{"id":"10.13039\/501100011019","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100015763","name":"Szegedi Tudom\u00e1nyegyetem","doi-asserted-by":"crossref","award":["OA 8344"],"award-info":[{"award-number":["OA 8344"]}],"id":[{"id":"10.13039\/501100015763","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n The emergence of drug-resistant\n Candida<\/jats:italic>\n species has created a demand for global antifungal strategies that extend beyond classical growth inhibition to target unknown vulnerabilities of fungal pathogens. In this study, we demonstrated that the\n Neosartorya<\/jats:italic>\n (\n Aspergillus<\/jats:italic>\n )\n fischeri<\/jats:italic>\n antifungal protein NFAP2 selectively targets early morphogenetic states of\n Candida albicans<\/jats:italic>\n and\n Candidozyma auris<\/jats:italic>\n , revealing a transient window of susceptibility during filament and pseudohypha formation. Integrated transcriptomic and\n in vivo<\/jats:italic>\n analyses indicate that these developmental states may represent context-dependent entry points for NFAP2 activity. In\n C. albicans<\/jats:italic>\n , transcriptomic and network analyses indicate the presence of an anabolic, translation-associated gene expression signature, accompanied by suppression of stress-protective pathways, which is associated with increased susceptibility of emerging hyphae to NFAP2 but does not establish a direct causal mechanism. In\n C. auris<\/jats:italic>\n , increased susceptibility of pseudohyphal cells occurred without overt transcriptional remodeling, consistent with the characteristically muted gene expression responses of this species, suggesting that NFAP2 sensitivity is governed primarily by biophysical and post-transcriptional mechanisms rather than transcriptional reprogramming. Importantly, morphotype-specific vulnerabilities observed\n in vitro<\/jats:italic>\n were reflected in distinct\n in vivo<\/jats:italic>\n outcomes in\n Galleria mellonella<\/jats:italic>\n , as NFAP2 was well tolerated and provided a moderate, transient survival benefit in pseudohyphal\n C. auris<\/jats:italic>\n infections, but not in filamentous\n C. albicans<\/jats:italic>\n , where a worsened outcome was observed, consistent with species- and morphotype-dependent activity. Taken together, these results suggest that early morphogenetic states of\n Candida<\/jats:italic>\n are stress-sensitive phenotypes associated with increased susceptibility to NFAP2. This work provides a proof-of-concept framework for future investigation of morphotype-associated antifungal vulnerability to peptide-based antifungal strategies.\n <\/jats:p>\n \n IMPORTANCE<\/jats:title>\n \n Drug-resistant\n Candida<\/jats:italic>\n species represent an escalating global health threat; however, most antifungal strategies continue to target fungal growth rather than intrinsic biological vulnerabilities. In this study, we identified early morphogenetic transitions as a shared window of increased susceptibility in both\n Candida albicans<\/jats:italic>\n and the highly drug-resistant pathogen\n Candidozyma<\/jats:italic>\n (formerly\n Candida<\/jats:italic>\n )\n auris<\/jats:italic>\n . By integrating transcriptomic profiling with\n in vivo<\/jats:italic>\n infection models, we found that NFAP2 exhibits antifungal activity that is influenced by these transient developmental states in a context-dependent manner while remaining well tolerated by the host. We further demonstrated that morphotype-specific stress responses are associated with the divergent sensitivities of\n C. albicans<\/jats:italic>\n and\n C. auris<\/jats:italic>\n to NFAP2. These results support the concept that fungal morphogenesis may represent a therapeutically actionable process and provide a framework for designing antifungal strategies that target developmental states rather than growth. This strategy may open new opportunities for improving protein- and peptide-based therapies, as well as combination therapies against difficult-to-treat fungal pathogens.\n <\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1128\/spectrum.00404-26","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:25:40Z","timestamp":1783344340000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Morphotype-specific susceptibility to\n Neosartorya<\/i>\n (\n Aspergillus<\/i>\n )\n fischeri<\/i>\n antifungal protein 2 is associated with an anabolic transcriptional signature in\n Candida<\/i>"],"prefix":"10.1128","volume":"14","author":[{"given":"Rich\u00e1rd","family":"Merber","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":"Doctoral School of Biology, Faculty of Science and Informatics, University of Szeged","place":["Szeged, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kriszti\u00e1n","family":"Laczi","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, Hungary"]},{"id":[{"id":"https:\/\/ror.org\/039h1gd08","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Plant Biology, HUN-REN Biological Research Centre","place":["Szeged, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4571-9775","authenticated-orcid":true,"given":"G\u00e1bor","family":"Bende","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, Hungary"]},{"id":[{"id":"https:\/\/ror.org\/01pnej532","id-type":"ROR","asserted-by":"publisher"}],"name":"Doctoral School of Biology, Faculty of Science and Informatics, University of Szeged","place":["Szeged, Hungary"]},{"id":[{"id":"https:\/\/ror.org\/01pnej532","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Theoretical Health Sciences and Health Management, Faculty of Health Sciences and Social Studies, University of Szeged","place":["Szeged, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Kazinczi","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, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Farkas","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/039h1gd08","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Plant Biology, HUN-REN Biological Research Centre","place":["Szeged, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gergely","family":"Mar\u00f3ti","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/039h1gd08","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Plant Biology, HUN-REN Biological Research Centre","place":["Szeged, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Sinka","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01pnej532","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Genetics, Faculty of Science and Informatics, University of Szeged","place":["Szeged, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6976-8910","authenticated-orcid":true,"given":"L\u00e1szl\u00f3","family":"Galg\u00f3czy","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, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","volume-title":"WHO fungal priority pathogens list to guide research, development and public health action","author":"World health organization","year":"2022","unstructured":"World health organization. 2022. 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