{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:45:19Z","timestamp":1760060719469,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["2022R1A6A3A01085818","NRF-RS-2024-00338026"],"award-info":[{"award-number":["2022R1A6A3A01085818","NRF-RS-2024-00338026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Aspergillus fumigatus is a major opportunistic pathogenic fungus that causes invasive aspergillosis with high mortality rates in immunocompromised patients. APSES family transcription factors regulate fungal development and virulence, but the function of the putative APSES-type transcription factor AfpA (AFUA_5g11390) remains uncharacterized. To investigate the roles of AfpA in A. fumigatus, we constructed the \u0394afpA mutant and performed phenotypic analyses, RT-qPCR analyses, and virulence studies. The \u0394afpA mutant exhibited reduced vegetative growth but increased conidiation, with upregulation of asexual developmental regulators brlA, abaA, and wetA. AfpA positively regulated cAMP-PKA signaling, resulting in delayed conidia germination. Furthermore, the mutant responded differently to external stresses and displayed enhanced virulence in neutropenic mice. In conclusion, AfpA functions as a multifaceted regulator balancing growth, development, and pathogenicity in A. fumigatus.<\/jats:p>","DOI":"10.3390\/jof11090678","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T08:56:46Z","timestamp":1758013006000},"page":"678","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Properties of Putative APSES Transcription Factor AfpA in Aspergillus fumigatus"],"prefix":"10.3390","volume":"11","author":[{"given":"Young-Ho","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Microbiology, Graduate School, Daejeon University, Daejeon 34520, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1241-6746","authenticated-orcid":false,"given":"Min-Woo","family":"Lee","sequence":"additional","affiliation":[{"name":"Soonchunhyang Institute of Medi-Bio Science, Soonchunhyang University, Cheonan 31151, Chungcheongnam-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7762-9593","authenticated-orcid":false,"given":"Kwang-Soo","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Graduate School, Daejeon University, Daejeon 34520, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1128\/CMR.12.2.310","article-title":"Aspergillus fumigatus and aspergillosis","volume":"12","author":"Latge","year":"1999","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1128\/CMR.00055-08","article-title":"Pathogenesis of Aspergillus fumigatus in Invasive Aspergillosis","volume":"22","author":"Dagenais","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5866","DOI":"10.1091\/mbc.e05-07-0617","article-title":"The Aspergillus fumigatus StuA protein governs the up-regulation of a discrete transcriptional program during the acquisition of developmental competence","volume":"16","author":"Sheppard","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e00998-20","DOI":"10.1128\/mSphere.00998-20","article-title":"The Putative APSES Transcription Factor RgdA Governs Growth, Development, Toxigenesis, and Virulence in Aspergillus fumigatus","volume":"5","author":"Jun","year":"2020","journal-title":"mSphere"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Choi, Y.H., Jun, S.C., Lee, M.W., Yu, J.H., and Shin, K.S. (2021). Characterization of the mbsA Gene Encoding a Putative APSES Transcription Factor in Aspergillus fumigatus. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073777"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lwin, H.P., Choi, Y.H., Lee, M.W., Yu, J.H., and Shin, K.S. (2019). RgsA Attenuates the PKA Signaling, Stress Response, and Virulence in the Human Opportunistic Pathogen Aspergillus fumigatus. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225628"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.fgb.2014.12.003","article-title":"The APSES family proteins in fungi: Characterizations, evolution and functions","volume":"81","author":"Zhao","year":"2015","journal-title":"Fungal Genet. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1534\/genetics.105.052258","article-title":"FluG-dependent asexual development in Aspergillus nidulans occurs via derepression","volume":"172","author":"Seo","year":"2006","journal-title":"Genetics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"RESEARCH0012","DOI":"10.1186\/gb-2002-3-3-research0012","article-title":"Extensive domain shuffling in transcription regulators of DNA viruses and implications for the origin of fungal APSES transcription factors","volume":"3","author":"Iyer","year":"2002","journal-title":"Genome Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.gde.2019.08.004","article-title":"Evolutionary innovation, fungal cell biology, and the lateral gene transfer of a viral KilA-N domain","volume":"58\u201359","author":"Medina","year":"2019","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/S1369-5274(00)00124-7","article-title":"Molecular genetics in Aspergillus fumigatus","volume":"3","author":"Brookman","year":"2000","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0065-2660(08)60245-X","article-title":"Meiotic and mitotic recombination in Aspergillus and its chromosomal aberrations","volume":"19","author":"Kafer","year":"1977","journal-title":"Adv. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.fgb.2004.08.001","article-title":"Double-joint PCR: A PCR-based molecular tool for gene manipulations in filamentous fungi","volume":"41","author":"Yu","year":"2004","journal-title":"Fungal Genet. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3111","DOI":"10.1038\/nprot.2006.405","article-title":"Fusion PCR and gene targeting in Aspergillus nidulans","volume":"1","author":"Szewczyk","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"701","DOI":"10.2116\/analsci.32.701","article-title":"Determination of Chitin Based on the Colorimetric Assay of Glucosamine in Acidic Hydrolysate","volume":"32","author":"Katano","year":"2016","journal-title":"Anal. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Choi, Y.H., Park, S.H., Kim, S.S., Lee, M.W., Yu, J.H., and Shin, K.S. (2023). Functional Characterization of the GNAT Family Histone Acetyltransferase Elp3 and GcnE in Aspergillus fumigatus. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032179"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1111\/j.1365-2958.2003.03940.x","article-title":"A putative G protein-coupled receptor negatively controls sexual development in Aspergillus nidulans","volume":"51","author":"Han","year":"2004","journal-title":"Mol. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.bbrc.2015.05.090","article-title":"Proteomic analyses reveal the key roles of BrlA and AbaA in biogenesis of gliotoxin in Aspergillus fumigatus","volume":"463","author":"Shin","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1128\/EC.00192-06","article-title":"Upstream and downstream regulation of asexual development in Aspergillus fumigatus","volume":"5","author":"Mah","year":"2006","journal-title":"Eukaryot. Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e3398","DOI":"10.7717\/peerj.3398","article-title":"Selection of housekeeping genes as internal controls for quantitative RT-PCR analysis of the veined rapa whelk (Rapana venosa)","volume":"5","author":"Song","year":"2017","journal-title":"PeerJ"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1266\/ggs.16-00007","article-title":"Assessment of housekeeping genes as internal references in quantitative expression analysis during early development of oyster","volume":"91","author":"Huan","year":"2017","journal-title":"Genes. Genet. Syst."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e00397-19","DOI":"10.1128\/mSphere.00397-19","article-title":"The Glycosylphosphatidylinositol-Anchored DFG Family Is Essential for the Insertion of Galactomannan into the \u03b2-(1,3)-Glucan-Chitin Core of the Cell Wall of Aspergillus fumigatus","volume":"4","author":"Muszkieta","year":"2019","journal-title":"mSphere"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3632","DOI":"10.1128\/IAI.01483-07","article-title":"In vivo analysis of Aspergillus fumigatus developmental gene expression determined by real-time reverse transcription-PCR","volume":"76","author":"Gravelat","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1099\/jmm.0.000450","article-title":"Characterization of the translation elongation factor 1-alpha gene in a wide range of pathogenic Aspergillus species","volume":"66","author":"Ahmadi","year":"2017","journal-title":"J. Med. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(\u2212\u0394\u0394C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1023\/B:BILE.0000019559.84305.47","article-title":"Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeper--Excel-based tool using pair-wise correlations","volume":"26","author":"Pfaffl","year":"2004","journal-title":"Biotechnol. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5193","DOI":"10.1128\/IAI.72.9.5193-5203.2004","article-title":"The cyclic AMP-dependent protein kinase a network regulates development and virulence in Aspergillus fumigatus","volume":"72","author":"Liebmann","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0003-2697(86)90200-9","article-title":"A double staining method for differentiating between two classes of mycobacterial catalase in polyacrylamide electrophoresis gels","volume":"157","author":"Wayne","year":"1986","journal-title":"Anal. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nprot.2009.197","article-title":"Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue","volume":"5","author":"Weydert","year":"2010","journal-title":"Nat. Protoc."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Choi, Y.H., Lee, M.W., and Shin, K.S. (2022). The Lysine Demethylases KdmA and KdmB Differently Regulate Asexual Development, Stress Response, and Virulence in Aspergillus fumigatus. J. Fungi, 8.","DOI":"10.3390\/jof8060590"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kwon, J.Y., Choi, Y.H., Lee, M.W., Yu, J.H., and Shin, K.S. (2023). The MYST Family Histone Acetyltransferase SasC Governs Diverse Biological Processes in Aspergillus fumigatus. Cells, 12.","DOI":"10.3390\/cells12222642"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e1005205","DOI":"10.1371\/journal.ppat.1005205","article-title":"Transcription Factor SomA Is Required for Adhesion, Development and Virulence of the Human Pathogen Aspergillus fumigatus","volume":"11","author":"Lin","year":"2015","journal-title":"PLoS Pathog."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1128\/IAI.71.2.891-903.2003","article-title":"Phagocytosis and intracellular fate of Aspergillus fumigatus conidia in alveolar macrophages","volume":"71","author":"Philippe","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2983","DOI":"10.1534\/g3.116.031112","article-title":"Aspergillus fumigatus MADS-Box Transcription Factor rlmA Is Required for Regulation of the Cell Wall Integrity and Virulence","volume":"6","author":"Rocha","year":"2016","journal-title":"G3 (Bethesda)"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1128\/EC.00293-13","article-title":"Transcription factor RFX1 is crucial for maintenance of genome integrity in Fusarium graminearum","volume":"13","author":"Min","year":"2014","journal-title":"Eukaryot. Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4923","DOI":"10.1128\/AEM.00470-08","article-title":"Protein kinase A regulates growth, sporulation, and pigment formation in Aspergillus fumigatus","volume":"74","author":"Grosse","year":"2008","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7364","DOI":"10.1093\/nar\/gkq617","article-title":"Genomic repertoires of DNA-binding transcription factors across the tree of life","volume":"38","author":"Charoensawan","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.isci.2018.09.003","article-title":"DNA Motif Recognition Modeling from Protein Sequences","volume":"7","author":"Wong","year":"2018","journal-title":"iScience"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"16143","DOI":"10.1073\/pnas.1818015116","article-title":"Homotypic cooperativity and collective binding are determinants of bHLH specificity and function","volume":"116","author":"Shively","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/1471-2148-12-154","article-title":"Accurate discrimination of bHLH domains in plants, animals, and fungi using biologically meaningful sites","volume":"12","author":"Sailsbery","year":"2012","journal-title":"BMC Evol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1093\/molbev\/msr288","article-title":"Phylogenetic analysis and classification of the fungal bHLH domain","volume":"29","author":"Sailsbery","year":"2012","journal-title":"Mol. Biol. Evol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1093\/genetics\/144.3.991","article-title":"Asm-1+, a Neurospora crassa gene related to transcriptional regulators of fungal development","volume":"144","author":"Aramayo","year":"1996","journal-title":"Genetics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1101\/gad.6.9.1770","article-title":"StuA is required for cell pattern formation in Aspergillus","volume":"6","author":"Miller","year":"1992","journal-title":"Genes. Dev."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Jiao, W., Li, M., Lei, T., Liu, X., Zhang, J., Hu, J., Zhang, X., Liu, J., Shi, S., and Pan, H. (2024). The APSES Transcription Factor SsStuA Regulating Cell Wall Integrity Is Essential for Sclerotia Formation and Pathogenicity in Sclerotinia sclerotiorum. J. Fungi, 10.","DOI":"10.3390\/jof10040238"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nrmicro.2017.90","article-title":"Aspergillus fumigatus morphology and dynamic host interactions","volume":"15","author":"Gresnigt","year":"2017","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"S181","DOI":"10.1080\/14789940500051417","article-title":"Immunity to Aspergillus fumigatus: The basis for immunotherapy and vaccination","volume":"43","author":"Bellocchio","year":"2005","journal-title":"Med. Mycol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.fgb.2015.04.007","article-title":"The G\u03b2-like protein CpcB is required for hyphal growth, conidiophore morphology and pathogenicity in Aspergillus fumigatus","volume":"81","author":"Cai","year":"2015","journal-title":"Fungal Genet. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1586\/eri.10.93","article-title":"Cracking the Toll-like receptor code in fungal infections","volume":"8","author":"Cunha","year":"2010","journal-title":"Expert. Rev. Anti Infect. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e1003080","DOI":"10.1371\/journal.ppat.1003080","article-title":"Innate sensing of chitin and chitosan","volume":"9","author":"Bueter","year":"2013","journal-title":"PLoS Pathog."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.coi.2008.10.002","article-title":"Chitin regulation of immune responses: An old molecule with new roles","volume":"20","author":"Lee","year":"2008","journal-title":"Curr. Opin. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3389\/fimmu.2014.00461","article-title":"Toll-like receptor signaling pathways","volume":"5","author":"Kawasaki","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/cmi.12249","article-title":"Signalling C-type lectin receptors, microbial recognition and immunity","volume":"16","author":"Hoving","year":"2014","journal-title":"Cell. Microbiol."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/11\/9\/678\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:46:11Z","timestamp":1760035571000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/11\/9\/678"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,16]]},"references-count":52,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["jof11090678"],"URL":"https:\/\/doi.org\/10.3390\/jof11090678","relation":{},"ISSN":["2309-608X"],"issn-type":[{"type":"electronic","value":"2309-608X"}],"subject":[],"published":{"date-parts":[[2025,9,16]]}}}