{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T08:49:33Z","timestamp":1788252573503,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pbio.3003341","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000}}],"reference-count":109,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R37AI066224"],"award-info":[{"award-number":["R37AI066224"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI172258-01A1"],"award-info":[{"award-number":["R01AI172258-01A1"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"crossref","award":["5R25GM056847"],"award-info":[{"award-number":["5R25GM056847"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["Graduate Research Fellowship"],"award-info":[{"award-number":["Graduate Research Fellowship"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Biohub San Francisco"}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>\n                    Adaptive responses to environmental stimuli are integral to the survival and virulence of microbial pathogens. The thermally dimorphic human fungal pathogen\n                    <jats:italic>Histoplasma<\/jats:italic>\n                    senses temperature to transition between a mold form in soil and a pathogenic yeast in mammalian hosts. The contributions of chromatin-modifying enzymes to the ability of\n                    <jats:italic>Histoplasma<\/jats:italic>\n                    to appropriately respond to temperature have never been explored. Through chemical inhibition and genetics, we determined that the class I histone deacetylase (HDAC)\n                    <jats:italic>RPD3<\/jats:italic>\n                    is required for normal\n                    <jats:italic>Histoplasma<\/jats:italic>\n                    yeast morphology at 37 \u00b0C. Rpd3 regulated the expression of key morphology-specific genes, including critical virulence factors and transcription factors (TFs), was required for normal DNA-binding activity of yeast-promoting TFs, and influenced histone acetylation levels at the loci of putative pro-filamentation TFs. Furthermore, Rpd3 was required for virulence in a macrophage model of infection. Taken together, Rpd3 is a critical regulatory component that both activates the pathogenesis program and represses the filamentation program to enable thermal dimorphism in\n                    <jats:italic>Histoplasma<\/jats:italic>\n                    . This work uncovers the crucial role that chromatin regulation plays in temperature response of this ubiquitous pathogen.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3003341","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T17:32:56Z","timestamp":1773768776000},"page":"e3003341","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Rpd3 histone deacetylase is a critical regulator of temperature-mediated morphogenesis and virulence in the human fungal pathogen Histoplasma"],"prefix":"10.1371","volume":"24","author":[{"given":"Nebat","family":"Ali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Voorhies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa A.","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3987-7534","authenticated-orcid":true,"given":"Anita","family":"Sil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"issue":"2","key":"pbio.3003341.ref001","doi-asserted-by":"crossref","first-page":"151","DOI":"10.3390\/jof7020151","article-title":"Endemic and other dimorphic mycoses in the Americas","volume":"7","author":"SR Lockhart","year":"2021","journal-title":"J Fungi (Basel)"},{"issue":"10","key":"pbio.3003341.ref002","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.3201\/eid2810.220046","article-title":"Molecular detection of Histoplasma capsulatum in Antarctica","volume":"28","author":"LM Moreira","year":"2022","journal-title":"Emerg Infect Dis"},{"issue":"1","key":"pbio.3003341.ref003","doi-asserted-by":"crossref","first-page":"2315960","DOI":"10.1080\/22221751.2024.2315960","article-title":"Tracing histoplasmosis genomic epidemiology and species occurrence across the USA","volume":"13","author":"BG Ten\u00f3rio","year":"2024","journal-title":"Emerg Microbes Infect"},{"issue":"10","key":"pbio.3003341.ref004","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.3201\/eid2410.180032","article-title":"Mapping Histoplasma capsulatum exposure, United States","volume":"24","author":"AW Maiga","year":"2018","journal-title":"Emerg Infect Dis"},{"issue":"5495","key":"pbio.3003341.ref005","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":"TS Sebghati","year":"2000","journal-title":"Science"},{"issue":"4","key":"pbio.3003341.ref006","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1128\/EC.00010-07","article-title":"Expression and interstrain variability of the YPS3 gene of Histoplasma capsulatum","volume":"6","author":"ML Bohse","year":"2007","journal-title":"Eukaryot Cell"},{"issue":"5","key":"pbio.3003341.ref007","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":"DT Isaac","year":"2015","journal-title":"Mol Microbiol"},{"issue":"9","key":"pbio.3003341.ref008","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":"BC English","year":"2017","journal-title":"PLoS Pathog"},{"issue":"6","key":"pbio.3003341.ref009","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":"D Azimova","year":"2022","journal-title":"PLoS Pathog"},{"key":"pbio.3003341.ref010","article-title":"A remarkable expansion of secreted cysteine knot proteins reveals novel virulence factors in the human fungal pathogen Histoplasma","author":"RA Rodriguez","year":"2025","journal-title":"Cell Reports"},{"issue":"10","key":"pbio.3003341.ref011","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1634\/theoncologist.12-10-1247","article-title":"FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma","volume":"12","author":"BS Mann","year":"2007","journal-title":"Oncologist"},{"issue":"4","key":"pbio.3003341.ref012","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1111\/bjh.13318","article-title":"Entinostat, a novel histone deacetylase inhibitor is active in B-cell lymphoma and enhances the anti-tumour activity of rituximab and chemotherapy agents","volume":"169","author":"S Frys","year":"2015","journal-title":"Br J Haematol"},{"key":"pbio.3003341.ref013","article-title":"SARC018-SPORE02: phase II study of mocetinostat administered with gemcitabine for patients with metastatic leiomyosarcoma with progression or relapse following prior treatment with gemcitabine-containing therapy","author":"E Choy","year":"2018","journal-title":"Sarcoma"},{"issue":"4","key":"pbio.3003341.ref014","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":"LH Hwang","year":"2008","journal-title":"PLoS Pathog"},{"issue":"7","key":"pbio.3003341.ref015","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":"ED Holbrook","year":"2013","journal-title":"Infect Immun"},{"issue":"4","key":"pbio.3003341.ref016","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1111\/febs.16999","article-title":"The influence of a copper efflux pump in Histoplasma capsulatum virulence","volume":"291","author":"D Moraes","year":"2024","journal-title":"FEBS J"},{"issue":"6","key":"pbio.3003341.ref017","doi-asserted-by":"crossref","DOI":"10.1128\/iai.00059-23","article-title":"Histoplasma capsulatum relies on tryptophan biosynthesis to proliferate within the macrophage phagosome","volume":"91","author":"Q Shen","year":"2023","journal-title":"Infect Immun"},{"key":"pbio.3003341.ref018","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1186\/1471-2164-14-695","article-title":"Histoplasma yeast and mycelial transcriptomes reveal pathogenic-phase and lineage-specific gene expression profiles","volume":"14","author":"JA Edwards","year":"2013","journal-title":"BMC Genomics"},{"issue":"6","key":"pbio.3003341.ref019","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":"DO Inglis","year":"2013","journal-title":"Eukaryot Cell"},{"issue":"9","key":"pbio.3003341.ref020","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1003799","article-title":"N-acetylglucosamine (GlcNAc) triggers a rapid, temperature-responsive morphogenetic program in thermally dimorphic fungi","volume":"9","author":"SA Gilmore","year":"2013","journal-title":"PLoS Genet"},{"key":"pbio.3003341.ref021","article-title":"Temperature-induced switch to the pathogenic yeast form of Histoplasma capsulatum requires Ryp1, a conserved transcriptional regulator","author":"VQ Nguyen","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"pbio.3003341.ref022","article-title":"Conserved factors Ryp2 and Ryp3 control cell morphology and infectious spore formation in the fungal pathogen Histoplasma capsulatum","author":"R Hanby Webster","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"issue":"7","key":"pbio.3003341.ref023","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":"S Beyhan","year":"2013","journal-title":"PLoS Biol"},{"issue":"7","key":"pbio.3003341.ref024","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":"SA Gilmore","year":"2015","journal-title":"PLoS Genet"},{"key":"pbio.3003341.ref025","article-title":"Chemical stimuli override a temperature-dependent morphological program by reprogramming the transcriptome of a fungal pathogen","author":"D Assa","year":"2023","journal-title":"bioRx"},{"issue":"8","key":"pbio.3003341.ref026","article-title":"Characterization of the APSES-family transcriptional regulators of Histoplasma capsulatum","volume":"18","author":"LVG Longo","year":"2018","journal-title":"FEMS Yeast Res"},{"issue":"1","key":"pbio.3003341.ref027","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1042\/EBC20180061","article-title":"Acetylation & Co: an expanding repertoire of histone acylations regulates chromatin and transcription","volume":"63","author":"CE Barnes","year":"2019","journal-title":"Essays Biochem"},{"issue":"1","key":"pbio.3003341.ref028","doi-asserted-by":"crossref","first-page":"3004","DOI":"10.1038\/s41467-019-11046-7","article-title":"Chemical genomics reveals histone deacetylases are required for core regulatory transcription","volume":"10","author":"BE Gryder","year":"2019","journal-title":"Nat Commun"},{"issue":"3","key":"pbio.3003341.ref029","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/nrm2346","article-title":"The Rpd3\/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men","volume":"9","author":"X-J Yang","year":"2008","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"7","key":"pbio.3003341.ref030","article-title":"Hyphal development in Candida albicans requires two temporally linked changes in promoter chromatin for initiation and maintenance","volume":"9","author":"Y Lu","year":"2011","journal-title":"PLoS Biol"},{"key":"pbio.3003341.ref031","doi-asserted-by":"crossref","first-page":"12916","DOI":"10.1038\/ncomms12916","article-title":"N-acetylglucosamine sensing by a GCN5-related N-acetyltransferase induces transcription via chromatin histone acetylation in fungi","volume":"7","author":"C Su","year":"2016","journal-title":"Nat Commun"},{"issue":"10","key":"pbio.3003341.ref032","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.3390\/genes12101470","article-title":"Fungal lysine deacetylases in virulence, resistance, and production of small bioactive compounds","volume":"12","author":"I Bauer","year":"2021","journal-title":"Genes (Basel)"},{"issue":"5","key":"pbio.3003341.ref033","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2009-10-5-r57","article-title":"The histone deacetylase Rpd3p is required for transient changes in genomic expression in response to stress","volume":"10","author":"AL Alejandro-Osorio","year":"2009","journal-title":"Genome Biol"},{"issue":"4","key":"pbio.3003341.ref034","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1111\/j.1365-2958.2010.07167.x","article-title":"The Rpd3L HDAC complex is essential for the heat stress response in yeast","volume":"76","author":"C Ruiz-Roig","year":"2010","journal-title":"Mol Microbiol"},{"issue":"3","key":"pbio.3003341.ref035","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1080\/15592294.2019.1664229","article-title":"Nut1\/Hos1 and Sas2\/Rpd3 control the H3 acetylation of two different sets of osmotic stress-induced genes","volume":"15","author":"ME P\u00e9rez-Mart\u00ednez","year":"2020","journal-title":"Epigenetics"},{"issue":"12","key":"pbio.3003341.ref036","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/nrg3055","article-title":"Controlling gene expression in response to stress","volume":"12","author":"E de Nadal","year":"2011","journal-title":"Nat Rev Genet"},{"issue":"6","key":"pbio.3003341.ref037","article-title":"The paralogous histone deacetylases Rpd3 and Rpd31 play opposing roles in regulating the white-opaque switch in the fungal pathogen Candida albicans","volume":"7","author":"J Xie","year":"2016","journal-title":"mBio"},{"issue":"5","key":"pbio.3003341.ref038","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000889","article-title":"The Set3\/Hos2 histone deacetylase complex attenuates cAMP\/PKA signaling to regulate morphogenesis and virulence of Candida albicans","volume":"6","author":"D Hnisz","year":"2010","journal-title":"PLoS Pathog"},{"issue":"3","key":"pbio.3003341.ref039","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01201-14","article-title":"A histone deacetylase complex mediates biofilm dispersal and drug resistance in Candida albicans","volume":"5","author":"CJ Nobile","year":"2014","journal-title":"mBio"},{"issue":"1","key":"pbio.3003341.ref040","doi-asserted-by":"crossref","first-page":"5209","DOI":"10.1038\/s41598-018-21965-y","article-title":"HDAC genes play distinct and redundant roles in Cryptococcus neoformans virulence","volume":"8","author":"F Brand\u00e3o","year":"2018","journal-title":"Sci Rep"},{"issue":"8","key":"pbio.3003341.ref041","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005134","article-title":"The Hos2 histone deacetylase controls ustilago maydis virulence through direct regulation of mating-type genes","volume":"11","author":"A El\u00edas-Villalobos","year":"2015","journal-title":"PLoS Pathog"},{"issue":"7","key":"pbio.3003341.ref042","article-title":"Pleiotropic effects of the histone deacetylase Hos2 linked to H4-K16 deacetylation, H3-K56 acetylation, and H2A-S129 phosphorylation in Beauveria bassiana","volume":"20","author":"Q Cai","year":"2018","journal-title":"Cell Microbiol"},{"issue":"11","key":"pbio.3003341.ref043","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1009185","article-title":"Opposing functions of Fng1 and the Rpd3 HDAC complex in H4 acetylation in Fusarium graminearum","volume":"16","author":"H Jiang","year":"2020","journal-title":"PLoS Genet"},{"key":"pbio.3003341.ref044","doi-asserted-by":"crossref","unstructured":"Lee S, El-Agamy Farh M, Lee J, Taek Oh Y, Cho E, Park J, et al. A histone deacetylase, Magnaporthe oryzae RPD3, regulates reproduction and pathogenic development in the rice blast fungus. 2021. Available from: http:\/\/hme.riceblast.snu.ac.kr","DOI":"10.1128\/mBio.02600-21"},{"issue":"12","key":"pbio.3003341.ref045","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1007\/s12275-015-5488-3","article-title":"Histone deacetylase-mediated morphological transition in Candida albicans","volume":"53","author":"J Kim","year":"2015","journal-title":"J Microbiol"},{"issue":"6","key":"pbio.3003341.ref046","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":"B Joehnk","year":"2023","journal-title":"mSphere"},{"key":"pbio.3003341.ref047","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkz365","article-title":"CHOPCHOP v3: expanding the CRISPR web toolbox beyond genome editing","volume":"47","author":"K Labun","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"pbio.3003341.ref048","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1186\/1471-2105-12-323","article-title":"RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome","volume":"12","author":"B Li","year":"2011","journal-title":"BMC Bioinformatics"},{"issue":"5","key":"pbio.3003341.ref049","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"NL Bray","year":"2016","journal-title":"Nat Biotechnol"},{"key":"pbio.3003341.ref050","doi-asserted-by":"crossref","DOI":"10.2202\/1544-6115.1027","article-title":"Linear models and empirical bayes methods for assessing differential expression in microarray experiments","volume":"3","author":"GK Smyth","year":"2004","journal-title":"Stat Appl Genet Mol Biol"},{"issue":"7","key":"pbio.3003341.ref051","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"ME Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"pbio.3003341.ref052","article-title":"Rapid gain and loss of a chromosome drives key morphology and virulence phenotypes in Histoplasma, a fungal pathogen of humans","author":"S Heater","year":"2025","journal-title":"bioRx"},{"key":"pbio.3003341.ref053","article-title":"Chromosome-level genome assembly of a human fungal pathogen reveals synteny among geographically distinct species","author":"M Voorhies","year":"2022","journal-title":"mBio"},{"key":"pbio.3003341.ref054","unstructured":"Li H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. 2013. Available from: http:\/\/arxiv.org\/abs\/1303.3997"},{"issue":"4","key":"pbio.3003341.ref055","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"B Langmead","year":"2012","journal-title":"Nat Methods"},{"issue":"9","key":"pbio.3003341.ref056","doi-asserted-by":"crossref","DOI":"10.1186\/gb-2008-9-9-r137","article-title":"Model-based analysis of ChIP-Seq (MACS)","volume":"9","author":"Y Zhang","year":"2008","journal-title":"Genome Biol"},{"key":"pbio.3003341.ref057","doi-asserted-by":"crossref","unstructured":"Gaspar JM. Improved peak-calling with MACS2. bioRx 2018. https:\/\/doi.org\/10.1101\/496521","DOI":"10.1101\/496521"},{"issue":"4","key":"pbio.3003341.ref058","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3003066","article-title":"Transcriptomic atlas throughout Coccidioides development reveals key phase-enriched transcripts of this important fungal pathogen","volume":"23","author":"CM Homer","year":"2025","journal-title":"PLoS Biol"},{"issue":"10","key":"pbio.3003341.ref059","article-title":"Accelerated profile HMM searches","volume":"7","author":"SR Eddy","year":"2011","journal-title":"PLoS Comput Biol"},{"issue":"2","key":"pbio.3003341.ref060","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1101\/gr.2821705","article-title":"ProbCons: probabilistic consistency-based multiple sequence alignment","volume":"15","author":"CB Do","year":"2005","journal-title":"Genome Res"},{"issue":"3","key":"pbio.3003341.ref061","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0009490","article-title":"FastTree 2 \u2013 approximately maximum-likelihood trees for large alignments","volume":"5","author":"MN Price","year":"2010","journal-title":"PLoS One"},{"key":"pbio.3003341.ref062","volume-title":"R: a language and environment for statistical computing","author":"R Core T","year":"2021"},{"key":"pbio.3003341.ref063","unstructured":"The NumPy Array: a structure for efficient numerical computation. 2011. Available from: http:\/\/docs.python.org"},{"issue":"3","key":"pbio.3003341.ref064","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1109\/MCSE.2007.55","article-title":"Matplotlib: a 2D graphics environment","volume":"9","author":"JD Hunter","year":"2007","journal-title":"Comput Sci Eng"},{"key":"pbio.3003341.ref065","unstructured":"P\u00e9rez F, Granger BE. IPython: a system for interactive scientific computing. Available from: https:\/\/www.python.org"},{"issue":"17","key":"pbio.3003341.ref066","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.1093\/bioinformatics\/bth349","article-title":"Java Treeview\u2014extensible visualization of microarray data","volume":"20","author":"AJ Saldanha","year":"2004","journal-title":"Bioinformatics"},{"issue":"1","key":"pbio.3003341.ref067","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":"T Decker","year":"1988","journal-title":"J Immunol Methods"},{"issue":"2","key":"pbio.3003341.ref068","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":"DT Isaac","year":"2013","journal-title":"Infect Immun"},{"issue":"7","key":"pbio.3003341.ref069","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"J Schindelin","year":"2012","journal-title":"Nat Methods"},{"issue":"18","key":"pbio.3003341.ref070","doi-asserted-by":"crossref","first-page":"3693","DOI":"10.1093\/nar\/25.18.3693","article-title":"Histone deacetylases, acetoin utilization proteins and acetylpolyamine amidohydrolases are members of an ancient protein superfamily","volume":"25","author":"DD Leipe","year":"1997","journal-title":"Nucleic Acids Res"},{"issue":"9","key":"pbio.3003341.ref071","article-title":"The histone code of the fungal genus Aspergillus uncovered by evolutionary and proteomic analyses","volume":"8","author":"X Zhang","year":"2022","journal-title":"Microb Genom"},{"issue":"4","key":"pbio.3003341.ref072","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1111\/mmi.13578","article-title":"Extensive functional redundancy in the regulation of Candida albicans drug resistance and morphogenesis by lysine deacetylases Hos2, Hda1, Rpd3 and Rpd31","volume":"103","author":"X Li","year":"2017","journal-title":"Mol Microbiol"},{"issue":"6","key":"pbio.3003341.ref073","doi-asserted-by":"crossref","first-page":"565","DOI":"10.3390\/jof8060565","article-title":"Regulatory roles of histone modifications in filamentous fungal pathogens","volume":"8","author":"Y Lai","year":"2022","journal-title":"J Fungi (Basel)"},{"issue":"11","key":"pbio.3003341.ref074","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005938","article-title":"Fungal KATs\/KDACs: a new highway to better antifungal drugs?","volume":"12","author":"K Kuchler","year":"2016","journal-title":"PLoS Pathogens"},{"issue":"6","key":"pbio.3003341.ref075","doi-asserted-by":"crossref","first-page":"2314","DOI":"10.1091\/mbc.e03-01-0027","article-title":"Identifying phase-specific genes in the fungal pathogen Histoplasma capsulatum using a genomic shotgun microarray","volume":"14","author":"L Hwang","year":"2003","journal-title":"Mol Biol Cell"},{"issue":"12","key":"pbio.3003341.ref076","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1109\/TVCG.2014.2346248","article-title":"UpSet: visualization of intersecting sets","volume":"20","author":"A Lex","year":"2014","journal-title":"IEEE Trans Vis Comput Graph"},{"issue":"4","key":"pbio.3003341.ref077","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a018713","article-title":"Erasers of histone acetylation: the histone deacetylase enzymes","volume":"6","author":"E Seto","year":"2014","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"9","key":"pbio.3003341.ref078","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3000168","article-title":"Opposing signaling pathways regulate morphology in response to temperature in the fungal pathogen Histoplasma capsulatum","volume":"17","author":"L Rodriguez","year":"2019","journal-title":"PLoS Biol"},{"issue":"3","key":"pbio.3003341.ref079","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3002060","article-title":"Retraction: Opposing signaling pathways regulate morphology in response to temperature in the fungal pathogen Histoplasma capsulatum","volume":"21","author":"L Rodriguez","year":"2023","journal-title":"PLOS Biology"},{"key":"pbio.3003341.ref080","article-title":"Cloning and analysis of mold-specific genes in the dimorphic fungus Histoplasma capsulatum","author":"X Tian","year":"2001","journal-title":"Gene"},{"issue":"2","key":"pbio.3003341.ref081","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1128\/EC.1.2.249-256.2002","article-title":"The mold-specific MS8 gene is required for normal hypha formation in the dimorphic pathogenic fungus Histoplasma capsulatum","volume":"1","author":"X Tian","year":"2002","journal-title":"Eukaryot Cell"},{"issue":"11","key":"pbio.3003341.ref082","doi-asserted-by":"crossref","first-page":"981","DOI":"10.3390\/jof7110981","article-title":"Deletion of the stress response gene DDR48 from Histoplasma capsulatum increases sensitivity to oxidative stress, increases susceptibility to antifungals, and decreases fitness in macrophages","volume":"7","author":"LT Blancett","year":"2021","journal-title":"J Fungi (Basel)"},{"issue":"2","key":"pbio.3003341.ref083","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1111\/j.1365-2958.2006.05257.x","article-title":"The Zn(II)2Cys6 putative transcription factor NosA controls fruiting body formation in Aspergillus nidulans","volume":"61","author":"K Vienken","year":"2006","journal-title":"Mol Microbiol"},{"issue":"5","key":"pbio.3003341.ref084","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1111\/j.1365-2958.2010.07282.x","article-title":"FlbC is a putative nuclear C2H2 transcription factor regulating development in Aspergillus nidulans","volume":"77","author":"N-J Kwon","year":"2010","journal-title":"Mol Microbiol"},{"issue":"3","key":"pbio.3003341.ref085","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.fgb.2007.09.008","article-title":"The Aspergillus nidulans esdC (early sexual development) gene is necessary for sexual development and is controlled by veA and a heterotrimeric G protein","volume":"45","author":"K-H Han","year":"2008","journal-title":"Fungal Genet Biol"},{"issue":"10","key":"pbio.3003341.ref086","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.fgb.2012.07.001","article-title":"VEA1 is required for cleistothecial formation and virulence in Histoplasma capsulatum","volume":"49","author":"MC Laskowski-Peak","year":"2012","journal-title":"Fungal Genet Biol"},{"key":"pbio.3003341.ref087","article-title":"Histone deacetylase activity of Rpd3 is important for transcriptional repression in vivo","author":"D Kadosh","year":"1998","journal-title":"Genes Dev"},{"key":"pbio.3003341.ref088","unstructured":"Morrison, et al. In preparation. 2025."},{"issue":"2","key":"pbio.3003341.ref089","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/S1097-2765(01)00301-X","article-title":"Highly specific antibodies determine histone acetylation site usage in yeast heterochromatin and euchromatin","volume":"8","author":"N Suka","year":"2001","journal-title":"Mol Cell"},{"key":"pbio.3003341.ref090","doi-asserted-by":"crossref","DOI":"10.1016\/S0092-8674(02)01048-6","article-title":"A thiol peroxidase is an H2O2 receptor and redox-transducer in gene activation prokaryotic OxyR and SoxR transcription factors that sense and transduce hydrogen peroxide (H2O2) and superoxide anion signals","volume":"111","author":"AS Delaunay","year":"2002","journal-title":"Cell"},{"issue":"2","key":"pbio.3003341.ref091","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/0012-1606(90)90215-5","article-title":"Conidium differentiation in Aspergillus nidulans wild-type and wet-white (wetA) mutant strains","volume":"138","author":"TC Sewall","year":"1990","journal-title":"Dev Biol"},{"issue":"1","key":"pbio.3003341.ref092","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1534\/genetics.116.190835","article-title":"Histone deacetylases with antagonistic roles in Saccharomyces cerevisiae heterochromatin formation","volume":"204","author":"DM Thurtle-Schmidt","year":"2016","journal-title":"Genetics"},{"issue":"4","key":"pbio.3003341.ref093","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1111\/febs.13389","article-title":"Histoplasma capsulatum surmounts obstacles to intracellular pathogenesis","volume":"283","author":"AL Garfoot","year":"2016","journal-title":"FEBS J"},{"issue":"3","key":"pbio.3003341.ref094","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1111\/mmi.15149","article-title":"\u201cWe\u2019ve got to get out\u201d \u2013 strategies of human pathogenic fungi to escape from phagocytes","volume":"121","author":"J Sonnberger","year":"2024","journal-title":"Mol Microbiol"},{"issue":"6972","key":"pbio.3003341.ref095","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/nature02258","article-title":"The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes","volume":"427","author":"E De Nadal","year":"2004","journal-title":"Nature"},{"issue":"1","key":"pbio.3003341.ref096","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1093\/nar\/gku1185","article-title":"The conserved histone deacetylase Rpd3 and its DNA binding subunit Ume6 control dynamic transcript architecture during mitotic growth and meiotic development","volume":"43","author":"A Lardenois","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pbio.3003341.ref097","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7164\/antibiotics.29.1","article-title":"A new antifungal antibiotic, trichostatin","volume":"29","author":"N Tsuji","year":"1976","journal-title":"J Antibiot (Tokyo)"},{"issue":"28","key":"pbio.3003341.ref098","doi-asserted-by":"crossref","first-page":"17174","DOI":"10.1016\/S0021-9258(17)44885-X","article-title":"Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A","volume":"265","author":"M Yoshida","year":"1990","journal-title":"J Biol Chem"},{"issue":"11","key":"pbio.3003341.ref099","doi-asserted-by":"crossref","first-page":"3532","DOI":"10.1128\/AAC.46.11.3532-3539.2002","article-title":"Histone deacetylase inhibitors enhance Candida albicans sensitivity to azoles and related antifungals: correlation with reduction in CDR and ERG upregulation","volume":"46","author":"WL Smith","year":"2002","journal-title":"Antimicrob Agents Chemother"},{"issue":"12","key":"pbio.3003341.ref100","doi-asserted-by":"crossref","first-page":"3797","DOI":"10.1128\/JCM.00618-09","article-title":"Activity of MGCD290, a Hos2 histone deacetylase inhibitor, in combination with azole antifungals against opportunistic fungal pathogens","volume":"47","author":"MA Pfaller","year":"2009","journal-title":"J Clin Microbiol"},{"issue":"4","key":"pbio.3003341.ref101","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.diagmicrobio.2014.11.008","article-title":"In vitro activity of a Hos2 deacetylase inhibitor, MGCD290, in combination with echinocandins against echinocandin-resistant Candida species","volume":"81","author":"MA Pfaller","year":"2015","journal-title":"Diagn Microbiol Infect Dis"},{"issue":"2","key":"pbio.3003341.ref102","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1021\/acs.jmedchem.0c01763","article-title":"Novel carboline fungal histone deacetylase (HDAC) inhibitors for combinational treatment of azole-resistant Candidiasis","volume":"64","author":"Z Li","year":"2021","journal-title":"J Med Chem"},{"issue":"8","key":"pbio.3003341.ref103","doi-asserted-by":"crossref","first-page":"4563","DOI":"10.1021\/acs.jafc.4c09039","article-title":"Novel 5-(trifluoromethyl)-1,2,4-oxadiazole-based pyrimidin-4-ether histone deacetylase inhibitors for controlling rust disease: design, synthesis, activity, and structure-activity relationship","volume":"73","author":"X-H Liu","year":"2025","journal-title":"J Agric Food Chem"},{"issue":"6","key":"pbio.3003341.ref104","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00831-16","article-title":"A class 1 histone deacetylase with potential as an antifungal target","volume":"7","author":"I Bauer","year":"2016","journal-title":"mBio"},{"issue":"2","key":"pbio.3003341.ref105","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0031223","article-title":"Persistence versus escape: Aspergillus terreus and Aspergillus fumigatus employ different strategies during interactions with macrophages","volume":"7","author":"S Slesiona","year":"2012","journal-title":"PLoS One"},{"key":"pbio.3003341.ref106","article-title":"Mucor circinelloides thrives inside the phagosome through an atf-mediated germination pathway","author":"C P\u00e9rez-Arques","year":"2019","journal-title":"mBio"},{"issue":"1","key":"pbio.3003341.ref107","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00433-12","article-title":"Candida albicans morphogenesis is not required for macrophage interleukin 1\u03b2 production","volume":"4","author":"M Wellington","year":"2012","journal-title":"mBio"},{"key":"pbio.3003341.ref108","doi-asserted-by":"crossref","first-page":"6741","DOI":"10.1038\/ncomms7741","article-title":"Global analysis of fungal morphology exposes mechanisms of host cell escape","volume":"6","author":"TR O\u2019Meara","year":"2015","journal-title":"Nat Commun"},{"key":"pbio.3003341.ref109","doi-asserted-by":"crossref","unstructured":"Eissenberg LG, Goldman WE, Schlesinger PH. Histoplasma capsulatum modulates the acidification of phagolysosomes. 1993.","DOI":"10.1084\/jem.177.6.1605"}],"updated-by":[{"DOI":"10.1371\/journal.pbio.3003341","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000}}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3003341","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T18:10:04Z","timestamp":1777572604000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3003341"}},"subtitle":[],"editor":[{"given":"Jessica","family":"Brown","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,3,17]]},"references-count":109,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.3003341","relation":{},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,17]]}}}