{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T08:30:28Z","timestamp":1765269028616,"version":"build-2065373602"},"reference-count":65,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32170203","SWU-XDJH202323","CSTB2022NSCQ-MSX0573"],"award-info":[{"award-number":["32170203","SWU-XDJH202323","CSTB2022NSCQ-MSX0573"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["32170203","SWU-XDJH202323","CSTB2022NSCQ-MSX0573"],"award-info":[{"award-number":["32170203","SWU-XDJH202323","CSTB2022NSCQ-MSX0573"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Chongqing, China","award":["32170203","SWU-XDJH202323","CSTB2022NSCQ-MSX0573"],"award-info":[{"award-number":["32170203","SWU-XDJH202323","CSTB2022NSCQ-MSX0573"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Cryptococcus neoformans is a globally distributed human fungal pathogen that can cause cryptococcal meningitis with high morbidity and mortality. In this study, we identified an anaphase-promoting complex (APC) activator, Cdh1, and examined its impact on the virulence of C. neoformans. Our subcellular localization analysis revealed that Cdh1 is situated in the nucleus of C. neoformans. Disrupting or overexpressing the CDH1 gene caused abnormal capsule formation in C. neoformans. The cdh1\u0394 mutant displayed slight sensitivity when grown at 37 \u00b0C, indicating that Cdh1 plays a role in maintaining the growth of C. neoformans at 37 \u00b0C. A fungal virulence assay showed that Cdh1 is closely associated with the virulence of C. neoformans, and both the cdh1\u0394 mutant and CDH1OE overexpression strains significantly diminished the virulence of C. neoformans. The Cryptococcus\u2013macrophage interaction assay revealed that both the cdh1\u2206 mutant and the CDH1OE strains had significantly lower proliferation ability inside macrophages. Furthermore, the infection of the cdh1\u0394 mutant significantly activated neutrophil recruitment, as well as Th2 and Th17 immune responses, in lung tissue. In summary, our findings indicate that Cdh1 is crucial for producing virulence factors and fungal virulence in C. neoformans. The findings of this study can offer valuable insights and form the basis for further study of the regulatory mechanisms governing the pathogenicity of C. neoformans, potentially leading to the development of novel therapeutic strategies.<\/jats:p>","DOI":"10.3390\/jof10120891","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T04:45:49Z","timestamp":1735015549000},"page":"891","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Role of the Anaphase-Promoting Complex Activator Cdh1 in the Virulence of Cryptococcus neoformans"],"prefix":"10.3390","volume":"10","author":[{"given":"Qiu-Hong","family":"Liao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Resource Insects, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lian-Tao","family":"Han","sequence":"additional","affiliation":[{"name":"Medical Research Institute, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng-Ru","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Resource Insects, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Li","family":"Fan","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9111-8826","authenticated-orcid":false,"given":"Tong-Bao","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Research Institute, Southwest University, Chongqing 400715, China"},{"name":"Jinfeng Laboratory, Chongqing 401329, China"},{"name":"Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1093\/infdis\/164.2.435","article-title":"Persistence of Cryptococcus neoformans in the Prostate: Failure of Fluconazole Despite High Doses","volume":"164","author":"Bailly","year":"1991","journal-title":"J. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1093\/clinids\/21.6.1510","article-title":"Cryptococcus neoformans myositis in a patient with AIDS","volume":"21","author":"Barber","year":"1995","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/S0190-9622(94)70094-X","article-title":"Cutaneous involvement with Cryptococcus neoformans in AIDS","volume":"30","author":"Durden","year":"1994","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1007\/s003450050167","article-title":"Fungal infections of the urinary tract","volume":"17","author":"Sobel","year":"1999","journal-title":"World J. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1172\/JCI41963","article-title":"Real-time imaging of trapping and urease-dependent transmigration of Cryptococcus neoformans in mouse brain","volume":"120","author":"Shi","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e428","DOI":"10.1016\/S1473-3099(23)00692-8","article-title":"Global incidence and mortality of severe fungal disease","volume":"24","author":"Denning","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e750","DOI":"10.1016\/S2352-3018(23)00174-1","article-title":"HIV and fungal priority pathogens","volume":"10","author":"Sati","year":"2023","journal-title":"Lancet HIV"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0065-2164(09)01204-0","article-title":"The capsule of the fungal pathogen Cryptococcus neoformans","volume":"68","author":"Zaragoza","year":"2009","journal-title":"Adv. Appl. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Srikanta, D., Yang, M., Williams, M., and Doering, T.L. (2011). A sensitive high-throughput assay for evaluating host-pathogen interactions in Cryptococcus neoformans infection. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022773"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Li, L.X., Rautengarten, C., Heazlewood, J.L., and Doering, T.L. (2018). Xylose donor transport is critical for fungal virulence. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006765"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1093\/glycob\/cww078","article-title":"Cryptococcus neoformans UGT1 encodes a UDP-Galactose\/UDP-GalNAc transporter","volume":"27","author":"Li","year":"2017","journal-title":"Glycobiology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e02319-17","DOI":"10.1128\/mBio.02319-17","article-title":"UDP-Glucuronic Acid Transport Is Required for Virulence of Cryptococcus neoformans","volume":"9","author":"Li","year":"2018","journal-title":"mBio"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"177","DOI":"10.5582\/ddt.2019.01047","article-title":"Induction of signal transduction pathways related to the pathogenicity of Cryptococcus neoformans in the host environment","volume":"13","author":"Matsumoto","year":"2019","journal-title":"Drug Discov. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Nosanchuk, J.D., Stark, R.E., and Casadevall, A. (2015). Fungal Melanin: What do We Know About Structure?. Front. Microbiol., 6.","DOI":"10.3389\/fmicb.2015.01463"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e02085-20","DOI":"10.1128\/mBio.02085-20","article-title":"Laccase Affects the Rate of Cryptococcus neoformans Nonlytic Exocytosis from Macrophages","volume":"11","author":"Sousa","year":"2020","journal-title":"mBio"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1348-0421.2003.tb03395.x","article-title":"Effects of melanin upon susceptibility of Cryptococcus to antifungals","volume":"47","author":"Ikeda","year":"2003","journal-title":"Microbiol. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1111\/febs.13229","article-title":"Cryptococcus gattii urease as a virulence factor and the relevance of enzymatic activity in cryptococcosis pathogenesis","volume":"282","author":"Feder","year":"2015","journal-title":"FEBS J."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chrisman, C.J., Albuquerque, P., Guimaraes, A.J., Nieves, E., and Casadevall, A. (2011). Phospholipids trigger Cryptococcus neoformans capsular enlargement during interactions with amoebae and macrophages. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002047"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1128\/IAI.03104-14","article-title":"Cryptococcal phospholipase B1 is required for intracellular proliferation and control of titan cell morphology during macrophage infection","volume":"83","author":"Evans","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1128\/IAI.72.4.2229-2239.2004","article-title":"Role of extracellular phospholipases and mononuclear phagocytes in dissemination of cryptococcosis in a murine model","volume":"72","author":"Santangelo","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4755","DOI":"10.1128\/iai.62.11.4755-4761.1994","article-title":"Pathogenesis of pulmonary Cryptococcus neoformans infection in the rat","volume":"62","author":"Goldman","year":"1994","journal-title":"Infect. Immun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1177\/0300060513504365","article-title":"Increased permeability of blood-brain barrier is mediated by serine protease during Cryptococcus meningitis","volume":"42","author":"Xu","year":"2014","journal-title":"J. Int. Med. Res."},{"key":"ref_23","first-page":"163","article-title":"Genomic Instability and Cancer","volume":"5","author":"Yao","year":"2014","journal-title":"J. Carcinog. Mutagen."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/jcb.20690","article-title":"Cell cycle control in breast cancer cells","volume":"97","author":"Caldon","year":"2006","journal-title":"J. Cell. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1182\/blood-2005-01-0034","article-title":"Cyclin D dysregulation: An early and unifying pathogenic event in multiple myeloma","volume":"106","author":"Bergsagel","year":"2005","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.phrs.2016.03.012","article-title":"Cyclin-dependent protein kinase inhibitors including palbociclib as anticancer drugs","volume":"107","author":"Roskoski","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1158\/0008-5472.CAN-13-2247","article-title":"Cyclin E1 deregulation occurs early in secretory cell transformation to promote formation of fallopian tube-derived high-grade serous ovarian cancers","volume":"74","author":"Karst","year":"2014","journal-title":"Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nrc2771","article-title":"A census of amplified and overexpressed human cancer genes","volume":"10","author":"Santarius","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s00294-017-0688-5","article-title":"Connecting virulence pathways to cell-cycle progression in the fungal pathogen Cryptococcus neoformans","volume":"63","author":"Kelliher","year":"2017","journal-title":"Curr. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kelliher, C.M., Leman, A.R., Sierra, C.S., and Haase, S.B. (2016). Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1006453"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e00945-14","DOI":"10.1128\/mBio.00945-14","article-title":"Capsule growth in Cryptococcus neoformans is coordinated with cell cycle progression","volume":"5","author":"Cordero","year":"2014","journal-title":"mBio"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Rodas, R., Trevijano-Contador, N., Rom\u00e1n, E., Janbon, G., Moyrand, F., Pla, J., Casadevall, A., and Zaragoza, O. (2015). Role of Cln1 during melanization of Cryptococcus neoformans. Front. Microbiol., 6.","DOI":"10.3389\/fmicb.2015.00798"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1007\/s11427-020-1697-3","article-title":"A cyclin protein governs the infectious and sexual life cycles of Cryptococcus neoformans","volume":"64","author":"Hu","year":"2021","journal-title":"Sci. China Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1126\/science.1222236","article-title":"Tackling human fungal infections","volume":"336","author":"Brown","year":"2012","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Scorzoni, L., de Paula, E.S.A.C., Marcos, C.M., Assato, P.A., de Melo, W.C., de Oliveira, H.C., Costa-Orlandi, C.B., Mendes-Giannini, M.J., and Fusco-Almeida, A.M. (2017). Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.00036"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3305","DOI":"10.1128\/jcm.31.12.3305-3309.1993","article-title":"Karyotyping of Cryptococcus neoformans as an epidemiological tool","volume":"31","author":"Perfect","year":"1993","journal-title":"J. Clin. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4831","DOI":"10.1128\/IAI.71.9.4831-4841.2003","article-title":"Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and alpha isolates","volume":"71","author":"Nielsen","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1251\/bpo68","article-title":"Experimental modulation of capsule size in Cryptococcus neoformans","volume":"6","author":"Zaragoza","year":"2004","journal-title":"Biol. Proced. Online"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1128\/EC.00004-11","article-title":"The F-Box protein Fbp1 regulates sexual reproduction and virulence in Cryptococcus neoformans","volume":"10","author":"Liu","year":"2011","journal-title":"Eukaryot. Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1128\/EC.2.5.1036-1045.2003","article-title":"Recapitulation of the sexual cycle of the primary fungal pathogen Cryptococcus neoformans var. gattii: Implications for an outbreak on Vancouver Island, Canada","volume":"2","author":"Fraser","year":"2003","journal-title":"Eukaryot. Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5729","DOI":"10.1128\/IAI.00896-08","article-title":"The Cryptococcus neoformans Rho-GDP dissociation inhibitor mediates intracellular survival and virulence","volume":"76","author":"Price","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.fgb.2019.01.002","article-title":"The Cys2His2 zinc finger protein Zfp1 regulates sexual reproduction and virulence in Cryptococcus neoformans","volume":"124","author":"Fan","year":"2019","journal-title":"Fungal Genet Biol"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Han, L., Wu, Y., Xiong, S., and Liu, T. (2023). Ubiquitin Degradation of the AICAR Transformylase\/IMP Cyclohydrolase Ade16 Regulates the Sexual Reproduction of Cryptococcus neoformans. J. Fungi, 9.","DOI":"10.20944\/preprints202305.0203.v1"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1006\/fgbi.1999.1180","article-title":"Gene disruption by biolistic transformation in serotype D strains of Cryptococcus neoformans","volume":"29","author":"Davidson","year":"2000","journal-title":"Fungal Genet. Biol."},{"key":"ref_45","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(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Aminnejad, M., Cogliati, M., Duan, S., Arabatzis, M., Tintelnot, K., Castaneda, E., Lazera, M., Velegraki, A., Ellis, D., and Sorrell, T.C. (2016). Identification and Characterization of VNI\/VNII and Novel VNII\/VNIV Hybrids and Impact of Hybridization on Virulence and Antifungal Susceptibility Within the C. neoformans\/C. gattii Species Complex. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0163955"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1128\/EC.00045-10","article-title":"Fungal homoserine kinase (thr1Delta) mutants are attenuated in virulence and die rapidly upon threonine starvation and serum incubation","volume":"9","author":"Kingsbury","year":"2010","journal-title":"Eukaryot. Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s10930-018-9785-7","article-title":"WD40 Repeat Proteins: Signalling Scaffold with Diverse Functions","volume":"37","author":"Jain","year":"2018","journal-title":"Protein J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"101415","DOI":"10.1016\/j.mycmed.2023.101415","article-title":"Direct antimicrobial effects of chemokines on Cryptococcus spp, with special emphasis on a \u2018CXC\u2019 chemokine","volume":"33","author":"Singh","year":"2023","journal-title":"J. Med. Mycol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6499","DOI":"10.1093\/emboj\/20.22.6499","article-title":"Activation of Cdh1-dependent APC is required for G1 cell cycle arrest and DNA damage-induced G2 checkpoint in vertebrate cells","volume":"20","author":"Sudo","year":"2001","journal-title":"EMBO J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.devcel.2019.09.005","article-title":"The G2-to-M Transition Is Ensured by a Dual Mechanism that Protects Cyclin B from Degradation by Cdc20-Activated APC\/C","volume":"51","author":"Moyle","year":"2019","journal-title":"Dev. Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/S0092-8674(00)80529-2","article-title":"Yeast Hct1 is a regulator of Clb2 cyclin proteolysis","volume":"90","author":"Schwab","year":"1997","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1126\/science.278.5337.460","article-title":"CDC20 and CDH1: A family of substrate-specific activators of APC-dependent proteolysis","volume":"278","author":"Visintin","year":"1997","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"11317","DOI":"10.1073\/pnas.96.20.11317","article-title":"Expression of the CDH1-associated form of the anaphase-promoting complex in postmitotic neurons","volume":"96","author":"Gieffers","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1091\/mbc.11.5.1555","article-title":"Mitotic regulation of the APC activator proteins CDC20 and CDH1","volume":"11","author":"Kramer","year":"2000","journal-title":"Mol. Biol. Cell"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Conn, B.N., and Wozniak, K.L. (2023). Innate Pulmonary Phagocytes and Their Interactions with Pathogenic Cryptococcus Species. J. Fungi, 9.","DOI":"10.3390\/jof9060617"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4593","DOI":"10.1128\/IAI.00798-10","article-title":"The chemokine receptor CXCR2 ligand KC (CXCL1) mediates neutrophil recruitment and is critical for development of experimental Lyme arthritis and carditis","volume":"78","author":"Ritzman","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.4049\/jimmunol.1401138","article-title":"CXCL1 contributes to host defense in polymicrobial sepsis via modulating T cell and neutrophil functions","volume":"193","author":"Jin","year":"2014","journal-title":"J. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1002\/eji.200323626","article-title":"Neutropenia alters lung cytokine production in mice and reduces their susceptibility to pulmonary cryptococcosis","volume":"33","author":"Mednick","year":"2003","journal-title":"Eur. J. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Wozniak, K.L., Kolls, J.K., and Wormley, F.L. (2012). Depletion of neutrophils in a protective model of pulmonary cryptococcosis results in increased IL-17A production by gammadelta T cells. BMC Immunol., 13.","DOI":"10.1186\/1471-2172-13-65"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/s41579-021-00511-0","article-title":"Treatment strategies for cryptococcal infection: Challenges, advances and future outlook","volume":"19","author":"Iyer","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Sun, S., Coelho, M.A., Heitman, J., and Nowrousian, M. (2019). Convergent evolution of linked mating-type loci in basidiomycete fungi. PLoS Genet., 15.","DOI":"10.1101\/626911"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1146\/annurev-genet-110410-132536","article-title":"Sex in fungi","volume":"45","author":"Ni","year":"2011","journal-title":"Annu. Rev. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4345","DOI":"10.1128\/IAI.00542-09","article-title":"Spores as infectious propagules of Cryptococcus neoformans","volume":"77","author":"Velagapudi","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Wu, T., Fan, C.L., Han, L.T., Guo, Y.B., and Liu, T.B. (2021). Role of F-box Protein Cdc4 in Fungal Virulence and Sexual Reproduction of Cryptococcus neoformans. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.806465"}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/10\/12\/891\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:58:29Z","timestamp":1760115509000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/10\/12\/891"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,23]]},"references-count":65,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["jof10120891"],"URL":"https:\/\/doi.org\/10.3390\/jof10120891","relation":{},"ISSN":["2309-608X"],"issn-type":[{"type":"electronic","value":"2309-608X"}],"subject":[],"published":{"date-parts":[[2024,12,23]]}}}