{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:16:29Z","timestamp":1790381789209,"version":"4.1.0"},"reference-count":108,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01AI172258-01A1"],"award-info":[{"award-number":["1R01AI172258-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R37AI066224"],"award-info":[{"award-number":["R37AI066224"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cell Reports"],"published-print":{"date-parts":[[2025,11]]},"DOI":"10.1016\/j.celrep.2025.116465","type":"journal-article","created":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T04:10:23Z","timestamp":1761365423000},"page":"116465","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"title":["Expansion of secreted cystine knot proteins reveals virulence factors in the human fungal pathogen Histoplasma"],"prefix":"10.1016","volume":"44","author":[{"given":"Rosa A.","family":"Rodriguez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinara","family":"Azimova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Voorhies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bevin C.","family":"English","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Symington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3987-7534","authenticated-orcid":false,"given":"Anita","family":"Sil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.celrep.2025.116465_bib1","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a006114","article-title":"Subversion of cell signaling by pathogens","volume":"4","author":"Alto","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"10.1016\/j.celrep.2025.116465_bib2","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22126484","article-title":"Manipulation of Host Cell Organelles by Intracellular Pathogens","volume":"22","author":"Kellermann","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.celrep.2025.116465_bib3","doi-asserted-by":"crossref","first-page":"6484","DOI":"10.1128\/microbiolspec.BAI-0022-2019","article-title":"Manipulation of Host Cell Organelles by Intracellular Pathogens","volume":"7","author":"Omotade","year":"2019","journal-title":"Microbiol. Spectr."},{"key":"10.1016\/j.celrep.2025.116465_bib4","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.tim.2020.02.010","article-title":"Microbial Effector Proteins - A Journey through the Proteolytic Landscape","volume":"28","author":"Langin","year":"2020","journal-title":"Trends Microbiol."},{"key":"10.1016\/j.celrep.2025.116465_bib5","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.mib.2020.03.002","article-title":"Gastrointestinal host-pathogen interaction in the age of microbiome research","volume":"53","author":"Tsolis","year":"2020","journal-title":"Curr. Opin. Microbiol."},{"key":"10.1016\/j.celrep.2025.116465_bib6","doi-asserted-by":"crossref","DOI":"10.3389\/fcimb.2020.595029","article-title":"Host Cell Targets of Released Lipid and Secreted Protein Effectors of Mycobacterium tuberculosis","volume":"10","author":"Augenstreich","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"10.1016\/j.celrep.2025.116465_bib7","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1038\/s41579-022-00763-4","article-title":"Immune evasion and provocation by Mycobacterium tuberculosis","volume":"20","author":"Chandra","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"10.1016\/j.celrep.2025.116465_bib8","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1001289","article-title":"Secreted bacterial effectors that inhibit host protein synthesis are critical for induction of the innate immune response to virulent Legionella pneumophila","volume":"7","author":"Fontana","year":"2011","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.celrep.2025.116465_bib9","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1080\/21505594.2021.1903199","article-title":"Pathogenicity and Virulence of Legionella: Intracellular replication and host response","volume":"12","author":"Chauhan","year":"2021","journal-title":"Virulence"},{"key":"10.1016\/j.celrep.2025.116465_bib10","doi-asserted-by":"crossref","DOI":"10.1128\/microbiolspec.VMBF-0012-2015","article-title":"Bacterial Secretion Systems: An Overview","volume":"4","author":"Green","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"10.1016\/j.celrep.2025.116465_bib11","doi-asserted-by":"crossref","DOI":"10.3390\/ijms232113433","article-title":"Fungal Effectoromics: A World in Constant Evolution","volume":"23","author":"Todd","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.celrep.2025.116465_bib12","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":"10.1016\/j.celrep.2025.116465_bib13","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00449-20","article-title":"Threats Posed by the Fungal Kingdom to Humans, Wildlife, and Agriculture","volume":"11","author":"Fisher","year":"2020","journal-title":"mBio"},{"key":"10.1016\/j.celrep.2025.116465_bib14","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.idc.2021.03.011","article-title":"Histoplasmosis","volume":"35","author":"Arauz","year":"2021","journal-title":"Infect Dis Clin North Am"},{"key":"10.1016\/j.celrep.2025.116465_bib15","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s12275-016-6044-5","article-title":"Revisiting old friends: Developments in understanding Histoplasma capsulatum pathogenesis","volume":"54","author":"Woods","year":"2016","journal-title":"J. Microbiol."},{"key":"10.1016\/j.celrep.2025.116465_bib16","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.3201\/eid2410.180032","article-title":"Mapping Histoplasma capsulatum Exposure, United States","volume":"24","author":"Maiga","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"10.1016\/j.celrep.2025.116465_bib17","doi-asserted-by":"crossref","DOI":"10.3390\/jof7020151","article-title":"Endemic and Other Dimorphic Mycoses in The Americas","volume":"7","author":"Lockhart","year":"2021","journal-title":"J. Fungi"},{"key":"10.1016\/j.celrep.2025.116465_bib18","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1128\/jb.41.5.563-579.1941","article-title":"Cultural Study of the Life-Cycle of Histoplasma capsulatum Darling 1906","volume":"41","author":"Conant","year":"1941","journal-title":"J. Bacteriol."},{"key":"10.1016\/j.celrep.2025.116465_bib19","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1128\/jb.87.1.33-38.1964","article-title":"Intracellular Behavior of Histoplasma Capsulatum","volume":"87","author":"Howard","year":"1964","journal-title":"J. Bacteriol."},{"key":"10.1016\/j.celrep.2025.116465_bib20","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1128\/jb.89.2.518-523.1965","article-title":"Intracellular Growth of Histoplasma Capsulatum","volume":"89","author":"Howard","year":"1965","journal-title":"J. Bacteriol."},{"key":"10.1016\/j.celrep.2025.116465_bib21","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1189\/jlb.0308154","article-title":"Histoplasma capsulatum manifests preferential invasion of phagocytic subpopulations in murine lungs","volume":"84","author":"Deepe","year":"2008","journal-title":"J. Leukoc. Biol."},{"key":"10.1016\/j.celrep.2025.116465_bib22","first-page":"157","article-title":"Histoplasma Capsulatum: Mechanisms for Pathogenesis","volume":"422","author":"Mittal","year":"2019","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"10.1016\/j.celrep.2025.116465_bib23","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.4049\/jimmunol.176.3.1806","article-title":"Human macrophages do not require phagosome acidification to mediate fungistatic\/fungicidal activity against Histoplasma capsulatum","volume":"176","author":"Newman","year":"2006","journal-title":"J. Immunol."},{"key":"10.1016\/j.celrep.2025.116465_bib24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mib.2017.10.003","article-title":"Differentiation of the fungus Histoplasma capsulatum into a pathogen of phagocytes","volume":"40","author":"Shen","year":"2017","journal-title":"Curr. Opin. Microbiol."},{"key":"10.1016\/j.celrep.2025.116465_bib25","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1080\/21505594.2019.1663596","article-title":"Sensing the heat and the host: Virulence determinants of Histoplasma capsulatum","volume":"10","author":"Beyhan","year":"2019","journal-title":"Virulence"},{"key":"10.1016\/j.celrep.2025.116465_bib26","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1111\/mmi.13168","article-title":"Macrophage cell death and transcriptional response are actively triggered by the fungal virulence factor Cbp1 during H. capsulatum infection","volume":"98","author":"Isaac","year":"2015","journal-title":"Mol. Microbiol."},{"key":"10.1016\/j.celrep.2025.116465_bib27","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1002713","article-title":"Extracellular superoxide dismutase protects Histoplasma yeast cells from host-derived oxidative stress","volume":"8","author":"Youseff","year":"2012","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.celrep.2025.116465_bib28","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1128\/IAI.00304-07","article-title":"RNA interference-mediated silencing of the YPS3 gene of Histoplasma capsulatum reveals virulence defects","volume":"75","author":"Bohse","year":"2007","journal-title":"Infect. Immun."},{"key":"10.1016\/j.celrep.2025.116465_bib29","doi-asserted-by":"crossref","first-page":"e01388","DOI":"10.1128\/mBio.01388-15","article-title":"The Eng1 \u03b2-Glucanase Enhances Histoplasma Virulence by Reducing \u03b2-Glucan Exposure","volume":"7","author":"Garfoot","year":"2016","journal-title":"mBio"},{"key":"10.1016\/j.celrep.2025.116465_bib30","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000044","article-title":"Histoplasma requires SID1, a member of an iron-regulated siderophore gene cluster, for host colonization","volume":"4","author":"Hwang","year":"2008","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.celrep.2025.116465_bib31","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.1128\/IAI.00173-13","article-title":"Redundant catalases detoxify phagocyte reactive oxygen and facilitate Histoplasma capsulatum pathogenesis","volume":"81","author":"Holbrook","year":"2013","journal-title":"Infect. Immun."},{"key":"10.1016\/j.celrep.2025.116465_bib32","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1007444","article-title":"Macrophage activation by IFN-\u03b3 triggers restriction of phagosomal copper from intracellular pathogens","volume":"14","author":"Shen","year":"2018","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.celrep.2025.116465_bib33","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1128\/EC.00069-13","article-title":"Comparative transcriptomics of infectious spores from the fungal pathogen Histoplasma capsulatum reveals a core set of transcripts that specify infectious and pathogenic states","volume":"12","author":"Inglis","year":"2013","journal-title":"Eukaryot. Cell"},{"key":"10.1016\/j.celrep.2025.116465_bib34","doi-asserted-by":"crossref","first-page":"5257","DOI":"10.1128\/iai.65.12.5257-5261.1997","article-title":"Calcium dependence and binding in cultures of Histoplasma capsulatum","volume":"65","author":"Batanghari","year":"1997","journal-title":"Infect. Immun."},{"key":"10.1016\/j.celrep.2025.116465_bib35","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1046\/j.1365-2958.1998.00697.x","article-title":"Histoplasma acquisition of calcium and expression of CBP1 during intracellular parasitism","volume":"27","author":"Batanghari","year":"1998","journal-title":"Mol. Microbiol."},{"key":"10.1016\/j.celrep.2025.116465_bib36","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1126\/science.290.5495.1368","article-title":"Intracellular parasitism by Histoplasma capsulatum: fungal virulence and calcium dependence","volume":"290","author":"Sebghati","year":"2000","journal-title":"Science"},{"key":"10.1016\/j.celrep.2025.116465_bib37","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1006589","article-title":"The transcription factor CHOP, an effector of the integrated stress response, is required for host sensitivity to the fungal intracellular pathogen Histoplasma capsulatum","volume":"13","author":"English","year":"2017","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.celrep.2025.116465_bib38","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.15252\/embr.201642195","article-title":"The integrated stress response","volume":"17","author":"Pakos-Zebrucka","year":"2016","journal-title":"EMBO Rep."},{"key":"10.1016\/j.celrep.2025.116465_bib39","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/S1097-2765(03)00105-9","article-title":"An integrated stress response regulates amino acid metabolism and resistance to oxidative stress","volume":"11","author":"Harding","year":"2003","journal-title":"Mol. Cell"},{"key":"10.1016\/j.celrep.2025.116465_bib40","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1038\/sj.emboj.7600596","article-title":"TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death","volume":"24","author":"Ohoka","year":"2005","journal-title":"EMBO J."},{"key":"10.1016\/j.celrep.2025.116465_bib41","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1010417","article-title":"Cbp1, a fungal virulence factor under positive selection, forms an effector complex that drives macrophage lysis","volume":"18","author":"Azimova","year":"2022","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.celrep.2025.116465_bib42","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s00294-020-01118-3","article-title":"Fungal effectors, the double edge sword of phytopathogens","volume":"67","author":"Pradhan","year":"2021","journal-title":"Curr. Genet."},{"key":"10.1016\/j.celrep.2025.116465_bib43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-phyto-011516-040249","article-title":"Cladosporium fulvum Effectors: Weapons in the Arms Race with Tomato","volume":"54","author":"de Wit","year":"2016","journal-title":"Annu. Rev. Phytopathol."},{"key":"10.1016\/j.celrep.2025.116465_bib44","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.3389\/fmicb.2019.02575","article-title":"Evolution of the Genes Encoding Effector Candidates Within Multiple Pathotypes of Magnaporthe oryzae","volume":"10","author":"Kim","year":"2019","journal-title":"Front. Microbiol."},{"key":"10.1016\/j.celrep.2025.116465_bib45","doi-asserted-by":"crossref","first-page":"600","DOI":"10.3389\/fmicb.2016.00600","article-title":"Elucidating the Role of Effectors in Plant-Fungal Interactions: Progress and Challenges","volume":"7","author":"Selin","year":"2016","journal-title":"Front. Microbiol."},{"key":"10.1016\/j.celrep.2025.116465_bib46","doi-asserted-by":"crossref","DOI":"10.1016\/j.micres.2020.126567","article-title":"Effector Biology of Biotrophic Plant Fungal Pathogens: Current Advances and Future Prospects","volume":"241","author":"Jaswal","year":"2020","journal-title":"Microbiol. Res."},{"key":"10.1016\/j.celrep.2025.116465_bib47","doi-asserted-by":"crossref","DOI":"10.1038\/srep38572","article-title":"Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability","volume":"6","author":"Karimi","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.celrep.2025.116465_bib48","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1146\/annurev.phyto.112408.132637","article-title":"Fungal effector proteins","volume":"47","author":"Stergiopoulos","year":"2009","journal-title":"Annu. Rev. Phytopathol."},{"key":"10.1016\/j.celrep.2025.116465_bib49","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0029847","article-title":"Using hierarchical clustering of secreted protein families to classify and rank candidate effectors of rust fungi","volume":"7","author":"Saunders","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.celrep.2025.116465_bib50","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1002\/pro.5560031022","article-title":"A common structural motif incorporating a cystine knot and a triple-stranded beta-sheet in toxic and inhibitory polypeptides","volume":"3","author":"Pallaghy","year":"1994","journal-title":"Protein Sci."},{"key":"10.1016\/j.celrep.2025.116465_bib51","doi-asserted-by":"crossref","first-page":"D314","DOI":"10.1093\/nar\/gkm939","article-title":"KNOTTIN: the knottin or inhibitor cystine knot scaffold in 2007","volume":"36","author":"Gracy","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.celrep.2025.116465_bib52","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0014-5793(97)00117-8","article-title":"The race-specific elicitor AVR9 of the tomato pathogen Cladosporium fulvum: a cystine knot protein","volume":"404","author":"Vervoort","year":"1997","journal-title":"FEBS Lett."},{"key":"10.1016\/j.celrep.2025.116465_bib53","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1094\/MPMI-4-052","article-title":"Cloning and characterization of cDNA of avirulence gene avr9 of the fungal pathogen Cladosporium fulvum, causal agent of tomato leaf mold","volume":"4","author":"van Kan","year":"1991","journal-title":"Mol. Plant Microbe Interact."},{"key":"10.1016\/j.celrep.2025.116465_bib54","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.jmb.2004.03.016","article-title":"A combined transmembrane topology and signal peptide prediction method","volume":"338","author":"Kall","year":"2004","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.celrep.2025.116465_bib55","doi-asserted-by":"crossref","first-page":"W429","DOI":"10.1093\/nar\/gkm256","article-title":"Advantages of combined transmembrane topology and signal peptide prediction--the Phobius web server","volume":"35","author":"Kall","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.celrep.2025.116465_bib56","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1005395","article-title":"Genome-Wide Reprogramming of Transcript Architecture by Temperature Specifies the Developmental States of the Human Pathogen Histoplasma","volume":"11","author":"Gilmore","year":"2015","journal-title":"PLoS Genet."},{"key":"10.1016\/j.celrep.2025.116465_bib57","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1001614","article-title":"A temperature-responsive network links cell shape and virulence traits in a primary fungal pathogen","volume":"11","author":"Beyhan","year":"2013","journal-title":"PLoS Biol."},{"key":"10.1016\/j.celrep.2025.116465_bib58","doi-asserted-by":"crossref","first-page":"3867","DOI":"10.1128\/IAI.66.8.3867-3873.1998","article-title":"Identification and characterization of a phase-specific, nuclear DNA binding protein from the dimorphic pathogenic fungus Histoplasma capsulatum","volume":"66","author":"Abidi","year":"1998","journal-title":"Infect. Immun."},{"key":"10.1016\/j.celrep.2025.116465_bib59","doi-asserted-by":"crossref","first-page":"4414","DOI":"10.1128\/IAI.01893-14","article-title":"Glycosylation and immunoreactivity of the Histoplasma capsulatum Cfp4 yeast-phase exoantigen","volume":"82","author":"Holbrook","year":"2014","journal-title":"Infect. Immun."},{"key":"10.1016\/j.celrep.2025.116465_bib60","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1128\/jcm.35.5.1071-1076.1997","article-title":"Molecular cloning and characterization of a recombinant Histoplasma capsulatum antigen for antibody-based diagnosis of human histoplasmosis","volume":"35","author":"Chandrashekar","year":"1997","journal-title":"J. Clin. Microbiol."},{"key":"10.1016\/j.celrep.2025.116465_bib61","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1021\/pr1011697","article-title":"Definition of the extracellular proteome of pathogenic-phase Histoplasma capsulatum","volume":"10","author":"Holbrook","year":"2011","journal-title":"J. Proteome Res."},{"key":"10.1016\/j.celrep.2025.116465_bib62","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1586\/14789450.2014.932251","article-title":"Cystine-knot peptides: emerging tools for cancer imaging and therapy","volume":"11","author":"Ackerman","year":"2014","journal-title":"Expert Rev. Proteomics"},{"key":"10.1016\/j.celrep.2025.116465_bib63","doi-asserted-by":"crossref","first-page":"7973","DOI":"10.1021\/bi0106639","article-title":"Solution structure of the squash trypsin inhibitor MCoTI-II. A new family for cyclic knottins","volume":"40","author":"Heitz","year":"2001","journal-title":"Biochemistry"},{"key":"10.1016\/j.celrep.2025.116465_bib64","doi-asserted-by":"crossref","first-page":"20699","DOI":"10.1074\/jbc.M109.003384","article-title":"The biological activity of the prototypic cyclotide kalata b1 is modulated by the formation of multimeric pores","volume":"284","author":"Huang","year":"2009","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.celrep.2025.116465_bib65","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2024.105682","article-title":"Scanning mutagenesis identifies residues that improve the long-term stability and insecticidal activity of cyclotide kalata B1","volume":"300","author":"Huang","year":"2024","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.celrep.2025.116465_bib66","doi-asserted-by":"crossref","first-page":"7565","DOI":"10.1021\/bi012000x","article-title":"Design, pharmacology, and NMR structure of a minimized cystine knot with agouti-related protein activity","volume":"41","author":"Jackson","year":"2002","journal-title":"Biochemistry"},{"key":"10.1016\/j.celrep.2025.116465_bib67","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/nature02632","article-title":"A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom","volume":"430","author":"Lee","year":"2004","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.116465_bib68","doi-asserted-by":"crossref","DOI":"10.3390\/pathogens12010143","article-title":"In Silico Analysis of a Drosophila Parasitoid Venom Peptide Reveals Prevalence of the Cation-Polar-Cation Clip Motif in Knottin Proteins","volume":"12","author":"Arguelles","year":"2023","journal-title":"Pathogens"},{"key":"10.1016\/j.celrep.2025.116465_bib69","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1096\/fj.02-1044fje","article-title":"Evolutionary origin of inhibitor cystine knot peptides","volume":"17","author":"Zhu","year":"2003","journal-title":"FASEB J."},{"key":"10.1016\/j.celrep.2025.116465_bib70","unstructured":"Mesarich, C., \u00d6kmen, B., R\u00f6venich, H. J., Karimi Jashni, M., Wang, C., Griffiths, S. A., Collemare, J. A. R., Deng, C., & de Wit, P. J. G. M. (2016). Novel effectors identified in the apoplast of Cladosporium fulvum-infected tomato."},{"key":"10.1016\/j.celrep.2025.116465_bib71","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1101\/gr.2361404","article-title":"Fosmid-based physical mapping of the Histoplasma capsulatum genome","volume":"14","author":"Magrini","year":"2004","journal-title":"Genome Res."},{"key":"10.1016\/j.celrep.2025.116465_bib72","unstructured":"Sil, A. (2004). Histoplasma G217B Genome (G217B_predicted.gff3). https:\/\/histo.ucsf.edu\/downloads\/G217B_predicted.gff3."},{"key":"10.1016\/j.celrep.2025.116465_bib73","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.02574-21","article-title":"Chromosome-Level Genome Assembly of a Human Fungal Pathogen Reveals Synteny among Geographically Distinct Species","volume":"13","author":"Voorhies","year":"2022","journal-title":"mBio"},{"key":"10.1016\/j.celrep.2025.116465_bib74","article-title":"Genome Dynamics and Chromosome Structural Variations in Histoplasma ohiense, a fungal pathogen of humans","author":"Heater","year":"2025","journal-title":"bioRxiv"},{"key":"10.1016\/j.celrep.2025.116465_bib75","doi-asserted-by":"crossref","first-page":"4473","DOI":"10.1038\/s41598-018-22816-6","article-title":"Genome analysis reveals evolutionary mechanisms of adaptation in systemic dimorphic fungi","volume":"8","author":"Munoz","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.celrep.2025.116465_bib76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13225-022-00506-z","article-title":"Phylogenetic and ecological reevaluation of the order","volume":"115","author":"Kandemir","year":"2022","journal-title":"Fungal Divers."},{"key":"10.1016\/j.celrep.2025.116465_bib77","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1101\/gr.087551.108","article-title":"Comparative genomic analyses of the human fungal pathogens Coccidioides and their relatives","volume":"19","author":"Sharpton","year":"2009","journal-title":"Genome Res."},{"key":"10.1016\/j.celrep.2025.116465_bib78","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1007977","article-title":"Emergomyces: The global rise of new dimorphic fungal pathogens","volume":"15","author":"Schwartz","year":"2019","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.celrep.2025.116465_bib79","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s13225-018-0403-y","article-title":"Phylogeny, ecology and taxonomy of systemic pathogens and their relatives in Ajellomycetaceae (Onygenales): Blastomyces, Emergomyces, Emmonsia, Emmonsiellopsis","volume":"90","author":"Jiang","year":"2018","journal-title":"Fungal Divers."},{"key":"10.1016\/j.celrep.2025.116465_bib80","doi-asserted-by":"crossref","first-page":"D439","DOI":"10.1093\/nar\/gkab1061","article-title":"AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models","volume":"50","author":"Varadi","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.celrep.2025.116465_bib81","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/978-1-0716-0892-0_14","article-title":"Protein Structure Modeling with MODELLER","volume":"2199","author":"Webb","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.celrep.2025.116465_bib82","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/pro.3280","article-title":"Improvements to the APBS biomolecular solvation software suite","volume":"27","author":"Jurrus","year":"2018","journal-title":"Protein Sci."},{"key":"10.1016\/j.celrep.2025.116465_bib83","doi-asserted-by":"crossref","first-page":"D454","DOI":"10.1093\/nar\/gkx1084","article-title":"KNOTTIN: the database of inhibitor cystine knot scaffold after 10 years, toward a systematic structure modeling","volume":"46","author":"Postic","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.celrep.2025.116465_bib84","doi-asserted-by":"crossref","first-page":"11199","DOI":"10.1074\/jbc.RA119.008817","article-title":"A knottin scaffold directs the CXC-chemokine-binding specificity of tick evasins","volume":"294","author":"Lee","year":"2019","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.celrep.2025.116465_bib85","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.peptides.2014.08.008","article-title":"YY-39, a tick anti-thrombosis peptide containing RGD domain","volume":"68","author":"Tang","year":"2015","journal-title":"Peptides"},{"key":"10.1016\/j.celrep.2025.116465_bib86","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1016\/j.ibmb.2005.05.007","article-title":"The transcriptome of the salivary glands of the female western black-legged tick Ixodes pacificus (Acari: Ixodidae)","volume":"35","author":"Francischetti","year":"2005","journal-title":"Insect Biochem. Mol. Biol."},{"key":"10.1016\/j.celrep.2025.116465_bib87","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3390\/toxins4050296","article-title":"Disintegrins from hematophagous sources","volume":"4","author":"Assumpcao","year":"2012","journal-title":"Toxins"},{"key":"10.1016\/j.celrep.2025.116465_bib88","doi-asserted-by":"crossref","DOI":"10.1128\/msphere.00370-23","article-title":"Recyclable CRISPR\/Cas9-mediated gene disruption and deletions in Histoplasma","volume":"8","author":"Joehnk","year":"2023","journal-title":"mSphere"},{"key":"10.1016\/j.celrep.2025.116465_bib89","doi-asserted-by":"crossref","DOI":"10.1128\/msphere.00178-23","article-title":"Targeted gene deletions in the dimorphic fungal pathogen Histoplasma using an optimized episomal CRISPR\/Cas9 system","volume":"8","author":"Rappleye","year":"2023","journal-title":"mSphere"},{"key":"10.1016\/j.celrep.2025.116465_bib90","doi-asserted-by":"crossref","DOI":"10.1038\/srep39401","article-title":"Identification and Characterization of Roseltide, a Knottin-type Neutrophil Elastase Inhibitor Derived from Hibiscus sabdariffa","volume":"6","author":"Loo","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.celrep.2025.116465_bib91","doi-asserted-by":"crossref","DOI":"10.3390\/ijms242417565","article-title":"Discovery and Characterization of MaK: A Novel Knottin Antimicrobial Peptide from Monochamus alternatus","volume":"24","author":"Han","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.celrep.2025.116465_bib92","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1186\/1471-2164-10-375","article-title":"ArachnoServer: a database of protein toxins from spiders","volume":"10","author":"Wood","year":"2009","journal-title":"BMC Genom."},{"key":"10.1016\/j.celrep.2025.116465_bib93","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/j.jmb.2004.12.030","article-title":"Structures of the agouti signaling protein","volume":"346","author":"McNulty","year":"2005","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.celrep.2025.116465_bib94","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1046\/j.1365-3024.2001.00403.x","article-title":"Anti-interleukin-8 activity of tick salivary gland extracts","volume":"23","author":"Hajnicka","year":"2001","journal-title":"Parasite Immunol."},{"key":"10.1016\/j.celrep.2025.116465_bib95","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1111\/j.1365-2958.2006.05436.x","article-title":"An alpha-(1,4)-amylase is essential for alpha-(1,3)-glucan production and virulence in Histoplasma capsulatum","volume":"62","author":"Marion","year":"2006","journal-title":"Mol. Microbiol."},{"key":"10.1016\/j.celrep.2025.116465_bib96","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1000069","article-title":"A probabilistic model of local sequence alignment that simplifies statistical significance estimation","volume":"4","author":"Eddy","year":"2008","journal-title":"PLoS Comput. Biol."},{"key":"10.1016\/j.celrep.2025.116465_bib97","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0009490","article-title":"FastTree 2--approximately maximum-likelihood trees for large alignments","volume":"5","author":"Price","year":"2010","journal-title":"PLoS One"},{"key":"10.1016\/j.celrep.2025.116465_bib98","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.116465_bib99","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1101\/gr.2821705","article-title":"ProbCons: Probabilistic consistency-based multiple sequence alignment","volume":"15","author":"Do","year":"2005","journal-title":"Genome Res."},{"key":"10.1016\/j.celrep.2025.116465_bib100","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1006\/jmbi.2000.5197","article-title":"Automatic clustering of orthologs and in-paralogs from pairwise species comparisons","volume":"314","author":"Remm","year":"2001","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.celrep.2025.116465_bib101","doi-asserted-by":"crossref","first-page":"W521","DOI":"10.1093\/nar\/gkae241","article-title":"The EMBL-EBI Job Dispatcher sequence analysis tools framework in 2024","volume":"52","author":"Madeira","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.celrep.2025.116465_bib102","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/msb.2011.75","article-title":"Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega","volume":"7","author":"Sievers","year":"2011","journal-title":"Mol. Syst. Biol."},{"key":"10.1016\/j.celrep.2025.116465_bib103","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1093\/molbev\/msu300","article-title":"IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies","volume":"32","author":"Nguyen","year":"2015","journal-title":"Mol. Biol. Evol."},{"key":"10.1016\/j.celrep.2025.116465_bib104","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1093\/molbev\/msx281","article-title":"UFBoot2: Improving the Ultrafast Bootstrap Approximation","volume":"35","author":"Hoang","year":"2018","journal-title":"Mol. Biol. Evol."},{"key":"10.1016\/j.celrep.2025.116465_bib105","first-page":"656","article-title":"BLAT--the BLAST-like alignment tool","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Res."},{"key":"10.1016\/j.celrep.2025.116465_bib106","doi-asserted-by":"crossref","first-page":"W547","DOI":"10.1093\/nar\/gkaf394","article-title":"The UniProt website API: facilitating programmatic access to protein knowledge","volume":"53","author":"Ahmad","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.celrep.2025.116465_bib107","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/0022-1759(88)90310-9","article-title":"A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity","volume":"115","author":"Decker","year":"1988","journal-title":"J. Immunol. Methods"},{"key":"10.1016\/j.celrep.2025.116465_bib108","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1128\/IAI.00833-12","article-title":"The 3-hydroxy-methylglutaryl coenzyme A lyase HCL1 is required for macrophage colonization by human fungal pathogen Histoplasma capsulatum","volume":"81","author":"Isaac","year":"2013","journal-title":"Infect. Immun."}],"container-title":["Cell Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211124725012367?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211124725012367?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:42:51Z","timestamp":1776919371000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2211124725012367"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":108,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["S2211124725012367"],"URL":"https:\/\/doi.org\/10.1016\/j.celrep.2025.116465","relation":{},"ISSN":["2211-1247"],"issn-type":[{"value":"2211-1247","type":"print"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Expansion of secreted cystine knot proteins reveals virulence factors in the human fungal pathogen Histoplasma","name":"articletitle","label":"Article Title"},{"value":"Cell Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.celrep.2025.116465","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"116465"}}