{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T17:51:30Z","timestamp":1782323490735,"version":"3.54.5"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81902083"],"award-info":[{"award-number":["81902083"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172294"],"award-info":[{"award-number":["82172294"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","award":["YX13400214"],"award-info":[{"award-number":["YX13400214"]}],"id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Laboratory of Basic Research on Regional Diseases (Guangxi Medical University), Education Department of Guangxi Zhuang Autonomous Region","award":["GXQYJB2024001"],"award-info":[{"award-number":["GXQYJB2024001"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Schistosomiasis remains a critical global health issue, necessitating novel therapies due to emerging praziquantel resistance. We previously developed a patented praziquantel derivative, DW-3\u201315, which demonstrated potent broad-spectrum schistosomicidal activity through\n                    <jats:italic>Sj<\/jats:italic>\n                    HAT1 inhibition. Here, the full-length\n                    <jats:italic>Sj<\/jats:italic>\n                    HAT1 cDNA is cloned by rapid amplification of cDNA ends methods. The protein encoded by the cDNA retains conserved catalytic residues of acetyltransferases although sharing 34% identity with mammalian orthologs. Enzyme activity analysis reveals that recombinant\n                    <jats:italic>Sj<\/jats:italic>\n                    HAT1 exhibits 130 \u03bcU\/mL histone acetyltransferase activity at 25\u00b0C for 60 min, and is completely inhibited by DW-3\u201315 at a concentration of 50 \u03bcM. However, DW-3\u201315 has no effect on the enzymatic activity of the human ortholog HAT1. Phylogenetic analyses place\n                    <jats:italic>Sj<\/jats:italic>\n                    HAT1 in a distinct clade, and molecular docking results indicate significant divergence compared to its human ortholog\n                    <jats:italic>Hs<\/jats:italic>\n                    HAT1. The expression profiling of\n                    <jats:italic>SjHAT1<\/jats:italic>\n                    reveals stage- and sex-specific patterns. Fluorescence\n                    <jats:italic>in situ<\/jats:italic>\n                    hybridization localizes\n                    <jats:italic>SjHAT1<\/jats:italic>\n                    predominantly in female vitellaria and male parenchyma near the gynecophoral canal. Knockdown of\n                    <jats:italic>SjHAT1<\/jats:italic>\n                    reduces worm survival by 57.5%\n                    <jats:italic>in vivo<\/jats:italic>\n                    , suppresses female oviposition by 90.8%\n                    <jats:italic>in vitro<\/jats:italic>\n                    and 79.2%\n                    <jats:italic>in vivo<\/jats:italic>\n                    , and disrupts ovarian and vitelline architecture. RNA-sequencing analysis reveals that\n                    <jats:italic>SjHAT1<\/jats:italic>\n                    knockdown disrupts \u03b2-alanyl-tryptamine (BATT) pheromone signaling via downregulation of\n                    <jats:italic>aromatic L-amino acid decarboxylase<\/jats:italic>\n                    (\n                    <jats:italic>AADC<\/jats:italic>\n                    ) in males and\n                    <jats:italic>multidrug resistance-associated protein 4<\/jats:italic>\n                    (\n                    <jats:italic>MRP4<\/jats:italic>\n                    ) in females. Given that BATT is essential for inducing female sexual development and egg production, the observed transcriptional dysregulation provides mechanistic evidence for disrupted intersexual communication. Our findings identify that\n                    <jats:italic>Sj<\/jats:italic>\n                    HAT1 is a central regulator of schistosome reproductive biology. These sex-specific mechanisms highlight\n                    <jats:italic>Sj<\/jats:italic>\n                    HAT1 as a potential therapeutic target for treatment and control of schistosomiasis.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014334","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T17:28:24Z","timestamp":1782322104000},"page":"e1014334","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Schistosoma japonicum histone acetyltransferase 1 (SjHAT1): A novel anti-schistosomal drug target"],"prefix":"10.1371","volume":"22","author":[{"given":"Jing","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Nan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Zheng","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3541-488X","authenticated-orcid":true,"given":"Chao-Ming","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"issue":"10479","key":"ppat.1014334.ref001","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/S0140-6736(24)02814-9","article-title":"Human schistosomiasis","volume":"405","author":"D Buonfrate","year":"2025","journal-title":"Lancet"},{"key":"ppat.1014334.ref002","author":"World Health Organization"},{"issue":"6511","key":"ppat.1014334.ref003","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1126\/science.abb7699","article-title":"Large-scale RNAi screening uncovers therapeutic targets in the parasite Schistosoma mansoni","volume":"369","author":"J Wang","year":"2020","journal-title":"Science"},{"issue":"3","key":"ppat.1014334.ref004","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s00281-020-00789-x","article-title":"Schistosomiasis-from immunopathology to vaccines","volume":"42","author":"DP McManus","year":"2020","journal-title":"Semin Immunopathol"},{"key":"ppat.1014334.ref005","article-title":"Extensive transmission and variation in a functional receptor for praziquantel resistance in endemic Schistosoma mansoni","author":"DJ Berger","year":"2024","journal-title":"bioRxiv"},{"key":"ppat.1014334.ref006","doi-asserted-by":"crossref","first-page":"933097","DOI":"10.3389\/fitd.2022.933097","article-title":"A review of the genetic determinants of praziquantel resistance in Schistosoma mansoni: Is praziquantel and intestinal schistosomiasis a perfect match?","volume":"3","author":"S Summers","year":"2022","journal-title":"Front Trop Dis"},{"issue":"13","key":"ppat.1014334.ref007","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1016\/j.bmc.2017.04.031","article-title":"Medicinal chemistry of antischistosomal drugs: Praziquantel and oxamniquine","volume":"25","author":"VBR da Silva","year":"2017","journal-title":"Bioorg Med Chem"},{"issue":"6","key":"ppat.1014334.ref008","doi-asserted-by":"crossref","first-page":"701","DOI":"10.4155\/fmc.15.11","article-title":"What is the mechanism of action of praziquantel and how might resistance strike?","volume":"7","author":"PM Cupit","year":"2015","journal-title":"Future Med Chem"},{"issue":"4","key":"ppat.1014334.ref009","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1016\/j.bmcl.2011.12.133","article-title":"Praziquantel derivatives exhibit activity against both juvenile and adult Schistosoma japonicum","volume":"22","author":"W Duan","year":"2012","journal-title":"Bioorg Med Chem Lett"},{"issue":"11","key":"ppat.1014334.ref010","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0112163","article-title":"An artemisinin derivative of praziquantel as an orally active antischistosomal agent","volume":"9","author":"L Dong","year":"2014","journal-title":"PLoS One"},{"issue":"1","key":"ppat.1014334.ref011","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/s13071-019-3442-7","article-title":"In vitro and in vivo activities of DW-3-15, a commercial praziquantel derivative, against Schistosoma japonicum","volume":"12","author":"X Wang","year":"2019","journal-title":"Parasit Vectors"},{"issue":"1","key":"ppat.1014334.ref012","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13071-021-05065-x","article-title":"Synergistic effect of combination chemotherapy with praziquantel and DW-3-15 for Schistosoma japonicum in vitro and in vivo","volume":"14","author":"Z-Y Yang","year":"2021","journal-title":"Parasit Vectors"},{"issue":"8","key":"ppat.1014334.ref013","article-title":"Schistosomicidal effects of histone acetyltransferase inhibitors against Schistosoma japonicum juveniles and adult worms in vitro","volume":"18","author":"J Xu","year":"2024","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1014334.ref014","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.cbpa.2020.05.008","article-title":"Targeting histone acetylation\/deacetylation in parasites: an update (2017-2020)","volume":"57","author":"R Fioravanti","year":"2020","journal-title":"Curr Opin Chem Biol"},{"issue":"2","key":"ppat.1014334.ref015","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/s12276-020-0382-4","article-title":"A short guide to histone deacetylases including recent progress on class II enzymes","volume":"52","author":"S-Y Park","year":"2020","journal-title":"Exp Mol Med"},{"key":"ppat.1014334.ref016","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jprot.2016.08.008","article-title":"Proteome-wide analysis of lysine acetylation in adult Schistosoma japonicum worm","volume":"148","author":"Y Hong","year":"2016","journal-title":"J Proteomics"},{"key":"ppat.1014334.ref017","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.3389\/fmicb.2017.02248","article-title":"Comparative analysis of proteome-wide lysine acetylation in juvenile and adult Schistosoma japonicum","volume":"8","author":"Q Li","year":"2017","journal-title":"Front Microbiol"},{"issue":"5","key":"ppat.1014334.ref018","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1004116","article-title":"Epigenetic changes modulate schistosome egg formation and are a novel target for reducing transmission of schistosomiasis","volume":"10","author":"VC Carneiro","year":"2014","journal-title":"PLoS Pathog"},{"key":"ppat.1014334.ref019","doi-asserted-by":"crossref","first-page":"317","DOI":"10.3389\/fgene.2014.00317","article-title":"Epigenetic control of gene function in schistosomes: a source of therapeutic targets?","volume":"5","author":"A Cabezas-Cruz","year":"2014","journal-title":"Front Genet"},{"issue":"5","key":"ppat.1014334.ref020","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/S0968-0004(97)01034-7","article-title":"GCN5-related histone N-acetyltransferases belong to a diverse superfamily that includes the yeast SPT10 protein","volume":"22","author":"AF Neuwald","year":"1997","journal-title":"Trends Biochem Sci"},{"issue":"23","key":"ppat.1014334.ref021","doi-asserted-by":"crossref","first-page":"8925","DOI":"10.1073\/pnas.1114117109","article-title":"Structural basis for substrate specificity and catalysis of human histone acetyltransferase 1","volume":"109","author":"H Wu","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"ppat.1014334.ref022","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.ijpara.2016.03.004","article-title":"Identification of new markers for the Schistosoma mansoni vitelline lineage","volume":"46","author":"J Wang","year":"2016","journal-title":"Int J Parasitol"},{"issue":"5","key":"ppat.1014334.ref023","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.02582-16","article-title":"Praziquantel for schistosomiasis: single-drug metabolism revisited, mode of action, and resistance","volume":"61","author":"N Vale","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"issue":"7","key":"ppat.1014334.ref024","article-title":"Small change, big difference: A promising praziquantel derivative designated P96 with broad-spectrum antischistosomal activity for chemotherapy of schistosomiasis japonica","volume":"17","author":"J Xu","year":"2023","journal-title":"PLoS Negl Trop Dis"},{"issue":"8","key":"ppat.1014334.ref025","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1007\/BF01022380","article-title":"Male-stimulated female maturation in Schistosoma: a review","volume":"12","author":"I Popiel","year":"1986","journal-title":"J Chem Ecol"},{"issue":"5","key":"ppat.1014334.ref026","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S1471-4922(01)01893-1","article-title":"Schistosome male-female interaction: induction of germ-cell differentiation","volume":"17","author":"W Kunz","year":"2001","journal-title":"Trends Parasitol"},{"issue":"1","key":"ppat.1014334.ref027","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1645\/0022-3395(2002)088[0003:PASASA]2.0.CO;2","article-title":"Presidential address. Sex and schistosomes: an interesting biological interplay with control implications","volume":"88","author":"PT LoVerde","year":"2002","journal-title":"J Parasitol"},{"key":"ppat.1014334.ref028","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.ijpara.2023.03.007","article-title":"MicroRNA-1 targets ribosomal protein genes to regulate the growth, development and reproduction of Schistosoma japonicum","volume":"53","author":"C Sun","year":"2023","journal-title":"Int J Parasitol"},{"issue":"9","key":"ppat.1014334.ref029","first-page":"759","article-title":"Susceptibility of Schistosoma japonicum to different developmental stages to praziquantel","volume":"100","author":"SH Xiao","year":"1987","journal-title":"Chin Med J (Engl)"},{"issue":"3","key":"ppat.1014334.ref030","first-page":"243","article-title":"Physiology of egg formation of Schistosoma japonicum (in Chinese)","volume":"20","author":"Y He","year":"1974","journal-title":"Acta Zool Sin"},{"issue":"5","key":"ppat.1014334.ref031","doi-asserted-by":"crossref","first-page":"831","DOI":"10.4269\/ajtmh.1956.5.831","article-title":"The relative egg producing capacity of Schistosoma mansoni and Schistosoma japonicum","volume":"5","author":"DV Moore","year":"1956","journal-title":"Am J Trop Med Hyg"},{"issue":"6","key":"ppat.1014334.ref032","doi-asserted-by":"crossref","DOI":"10.1128\/msphere.00299-23","article-title":"Histone acetyltransferase Gcn5-mediated histone H3 acetylation facilitates cryptococcal morphogenesis and sexual reproduction","volume":"8","author":"M Chen","year":"2023","journal-title":"mSphere"},{"issue":"7","key":"ppat.1014334.ref033","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1002\/chem.201204291","article-title":"[(\u03b7(6)-Praziquantel)Cr(CO)3] derivatives with remarkable in vitro anti-schistosomal activity","volume":"19","author":"M Patra","year":"2013","journal-title":"Chemistry"},{"issue":"1367","key":"ppat.1014334.ref034","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1126\/science.53.1367.226","article-title":"Sex in the trematode family Schistosomidae","volume":"53","author":"WW Cort","year":"1921","journal-title":"Science"},{"issue":"284","key":"ppat.1014334.ref035","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1242\/jcs.s2-71.284.653","article-title":"Sex studies of Schistosoma japonicum","author":"AE Severinghaus","year":"1928","journal-title":"J Cell Sci"},{"issue":"4","key":"ppat.1014334.ref036","doi-asserted-by":"crossref","first-page":"535","DOI":"10.2307\/3280487","article-title":"Morphology and reproductive organs and oogenesis in bisexual and unisexual transplants of mature Schistosoma mansoni females","volume":"67","author":"ER Clough","year":"1981","journal-title":"J Parasitol"},{"issue":"5","key":"ppat.1014334.ref037","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3000254","article-title":"Systematically improved in vitro culture conditions reveal new insights into the reproductive biology of the human parasite Schistosoma mansoni","volume":"17","author":"J Wang","year":"2019","journal-title":"PLoS Biol"},{"issue":"9","key":"ppat.1014334.ref038","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2022.03.017","article-title":"A male-derived nonribosomal peptide pheromone controls female schistosome development","volume":"185","author":"R Chen","year":"2022","journal-title":"Cell"},{"issue":"12","key":"ppat.1014334.ref039","doi-asserted-by":"crossref","first-page":"4445","DOI":"10.1007\/s00253-022-12028-4","article-title":"Aromatic L-amino acid decarboxylases: mechanistic features and microbial applications","volume":"106","author":"S-W Han","year":"2022","journal-title":"Appl Microbiol Biotechnol"},{"issue":"26","key":"ppat.1014334.ref040","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2321349121","article-title":"A niche-derived nonribosomal peptide triggers planarian sexual development","volume":"121","author":"M Issigonis","year":"2024","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"ppat.1014334.ref041","doi-asserted-by":"crossref","first-page":"110525","DOI":"10.1016\/j.celrep.2022.110525","article-title":"Somatic regulation of female germ cell regeneration and development in planarians","volume":"38","author":"UW Khan","year":"2022","journal-title":"Cell Rep"},{"key":"ppat.1014334.ref042","doi-asserted-by":"crossref","first-page":"14693","DOI":"10.1038\/ncomms14693","article-title":"Dynamic transcriptomes identify biogenic amines and insect-like hormonal regulation for mediating reproduction in Schistosoma japonicum","volume":"8","author":"J Wang","year":"2017","journal-title":"Nat Commun"},{"issue":"8","key":"ppat.1014334.ref043","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.pt.2009.05.003","article-title":"The schistosome excretory system: a key to regulation of metabolism, drug excretion and host interaction","volume":"25","author":"JR Kusel","year":"2009","journal-title":"Trends Parasitol"},{"issue":"12","key":"ppat.1014334.ref044","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0001425","article-title":"Genetic knockdown and pharmacological inhibition of parasite multidrug resistance transporters disrupts egg production in Schistosoma mansoni","volume":"5","author":"RS Kasinathan","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"issue":"4","key":"ppat.1014334.ref045","doi-asserted-by":"crossref","first-page":"483","DOI":"10.4269\/ajtmh.1967.16.483","article-title":"An improved perfusion technique for recovering adult schistosomes from laboratory animals","volume":"16","author":"RH Duvall","year":"1967","journal-title":"Am J Trop Med Hyg"},{"issue":"1","key":"ppat.1014334.ref046","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s13071-024-06191-y","article-title":"An improved medium for in vitro studies of female reproduction and oviposition in Schistosoma japonicum","volume":"17","author":"Y You","year":"2024","journal-title":"Parasit Vectors"},{"issue":"8016","key":"ppat.1014334.ref047","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"J Abramson","year":"2024","journal-title":"Nature"},{"key":"ppat.1014334.ref048","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1107\/S0907444909042073","article-title":"MolProbity: all-atom structure validation for macromolecular crystallography","volume":"66","author":"VB Chen","year":"2010","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"1","key":"ppat.1014334.ref049","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/prot.70059","article-title":"Alternative conformation prediction using deep learning with multi-MSA strategy and structural clustering in CASP16","volume":"94","author":"Q Wuyun","year":"2026","journal-title":"Proteins"},{"issue":"2","key":"ppat.1014334.ref050","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/s41592-023-02130-4","article-title":"Improving deep learning protein monomer and complex structure prediction using DeepMSA2 with huge metagenomics data","volume":"21","author":"W Zheng","year":"2024","journal-title":"Nat Methods"},{"issue":"1","key":"ppat.1014334.ref051","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1128\/AAC.01900-13","article-title":"Evaluation of the anti-Schistosoma mansoni activity of thiosemicarbazones and thiazoles","volume":"58","author":"E de F Santiago","year":"2014","journal-title":"Antimicrob Agents Chemother"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014334","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T17:28:32Z","timestamp":1782322112000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1014334"}},"subtitle":[],"editor":[{"given":"Mostafa","family":"Zamanian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":51,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1014334","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,24]]}}}