{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:22:59Z","timestamp":1785424979048,"version":"3.56.0"},"reference-count":66,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["11J8122N"],"award-info":[{"award-number":["11J8122N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1S91118N, 1271225N"],"award-info":[{"award-number":["1S91118N, 1271225N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004497","name":"Onderzoeksraad, KU Leuven","doi-asserted-by":"publisher","award":["C14\/22\/075"],"award-info":[{"award-number":["C14\/22\/075"]}],"id":[{"id":"10.13039\/501100004497","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM124594, R35GM156045"],"award-info":[{"award-number":["R35GM124594, R35GM156045"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2025,10,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The Hxk1 protein of\n                      <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                      phosphorylates N-acetylglucosamine (GlcNAc) which is necessary for various cellular functions, including energy production and chitin synthesis. Further, this protein also regulates morphogenesis independently of its role in GlcNAc catabolism. When\n                      <jats:italic toggle=\"yes\">HXK1<\/jats:italic>\n                      is deleted, cells are hyperfilamentous on serum-containing medium. Furthermore, Hxk1 translocates to the nucleus in the presence of glucose. To gain a broad understanding of the effect of Hxk1 on gene expression in\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      , we performed genome-wide transcriptional profiling of the\n                      <jats:italic toggle=\"yes\">hxk1<\/jats:italic>\n                      mutant strain by RNA-Seq. The analysis of these RNA-Seq data showed that Hxk1 affects gene expression in both a carbon source-dependent and -independent manner. However, the effect on gene expression occurs via an indirect mechanism, as genome-wide CUT&amp;RUN binding experiments demonstrated that Hxk1 does not bind to the upstream intergenic regions of the differentially expressed genes. Deletion of\n                      <jats:italic toggle=\"yes\">HXK1<\/jats:italic>\n                      not only resulted in differences in gene expression of genes present in the GlcNAc and galactose regulons, but also in glucose transporter genes, including\n                      <jats:italic toggle=\"yes\">HGT13<\/jats:italic>\n                      . Hxk1 also negatively influences the expression of virulence-associated genes, including\n                      <jats:italic toggle=\"yes\">HWP1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">BRG1<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">UME6<\/jats:italic>\n                      . Consequently, an\n                      <jats:italic toggle=\"yes\">hxk1<\/jats:italic>\n                      mutant strain showed higher toxicity toward gut epithelial cells compared to the WT strain. Furthermore, the\n                      <jats:italic toggle=\"yes\">hxk1<\/jats:italic>\n                      mutant strain had higher expression levels of\n                      <jats:italic toggle=\"yes\">SOD4<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">SOD5<\/jats:italic>\n                      and showed higher resistance toward H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      . These findings highlight the multiple functions of Hxk1 in different cellular processes.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                        is a fungus that lives in the human body but does not cause any harm in healthy individuals. However, when the immune system is weakened,\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        can spread via the bloodstream all over the body and can lead to severe illness and even death. To infect the human body, multiple proteins hold distinct functions. Hxk1 is one of these proteins. This protein is involved in N-acetylglucosamine (GlcNAc) phosphorylation, as well as hyphae formation and glucose transport. To obtain a complete view of the processes regulated by Hxk1, we performed an RNA-Seq experiment. These data revealed that Hxk1 influences the regulation of genes involved in metabolic and virulence-related processes, such as GlcNAc metabolism, sterol metabolism, and oxidative stress resistance. These findings are important to better understand how\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        adapted itself to infect the host.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00395-25","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T12:04:53Z","timestamp":1758801893000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["<i>Candida albicans<\/i>\n                    Hxk1 influences expression of metabolic- and virulence-related genes"],"prefix":"10.1128","volume":"10","author":[{"given":"Stefanie","family":"Wijnants","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Cell Biology, Department of Biology, Institute of Botany and Microbiology, KU Leuven","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1767-0831","authenticated-orcid":true,"given":"Dimitrios","family":"Sofras","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biology, Department of Biology, Institute of Botany and Microbiology, KU Leuven","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"Van Genechten","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biology, Department of Biology, Institute of Botany and Microbiology, KU Leuven","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudy","family":"Vergauwen","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biology, Department of Biology, Institute of Botany and Microbiology, KU Leuven","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Valle Arevalo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00d9ah105","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Cell Biology, School of Natural Sciences, University of California Merced","place":["Merced, USA"]},{"id":[{"id":"https:\/\/ror.org\/00d9ah105","id-type":"ROR","asserted-by":"publisher"}],"name":"Quantitative and Systems Biology Graduate Program, University of California","place":["Merced, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepika","family":"Gunasekaran","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00d9ah105","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Cell Biology, School of Natural Sciences, University of California Merced","place":["Merced, USA"]},{"id":[{"id":"https:\/\/ror.org\/00d9ah105","id-type":"ROR","asserted-by":"publisher"}],"name":"Quantitative and Systems Biology Graduate Program, University of California","place":["Merced, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig L.","family":"Ennis","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00d9ah105","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Cell Biology, School of Natural Sciences, University of California Merced","place":["Merced, USA"]},{"id":[{"id":"https:\/\/ror.org\/00d9ah105","id-type":"ROR","asserted-by":"publisher"}],"name":"Quantitative and Systems Biology Graduate Program, University of California","place":["Merced, USA"]},{"id":[{"id":"https:\/\/ror.org\/00d9ah105","id-type":"ROR","asserted-by":"publisher"}],"name":"Health Sciences Research Institute, University of California Merced","place":["Merced, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Jenull","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05n3x4p02","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Medical Biochemistry, Max Perutz Labs Vienna, Campus Vienna Biocenter, Medical University of Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2719-5955","authenticated-orcid":true,"given":"Karl","family":"Kuchler","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05n3x4p02","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Medical Biochemistry, Max Perutz Labs Vienna, Campus Vienna Biocenter, Medical University of Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0799-6499","authenticated-orcid":true,"given":"Clarissa J.","family":"Nobile","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00d9ah105","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Cell Biology, School of Natural Sciences, University of California Merced","place":["Merced, USA"]},{"id":[{"id":"https:\/\/ror.org\/00d9ah105","id-type":"ROR","asserted-by":"publisher"}],"name":"Health Sciences Research Institute, University of California Merced","place":["Merced, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1542-897X","authenticated-orcid":true,"given":"Patrick","family":"Van Dijck","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Cell Biology, Department of Biology, Institute of Botany and Microbiology, KU Leuven","place":["Leuven, Belgium"]},{"name":"KU Leuven One Health Institute","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/MCC.0b013e32833e84d2"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.4161\/viru.22913"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03390.x"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2021.10.003"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.9.2632-2639.1993"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.174.21.6789-6799.1992"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2020.11427"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2014.00066"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.2174\/187152606779025815"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.810440"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04771.x"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2022.127146"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00357-17"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/250344a0"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3340856"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.6064\/2012\/489208"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)60444-2"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053638"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.249854"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12916"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.01274"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2016.05.001"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.01.123"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000612"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-63308-w"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00328721"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2008.06528.x"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0065-2911(08)60110-1"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj1780427"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.176.9.2640-2647.1994"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/mbo3.274"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e06-10-0931"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.250452997"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyaa012"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2021.08.013"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1937-6448(08)01003-4"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00186-06"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2016.1188236"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.8.2404-2412.2003"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2008.01274.x"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00094"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens8020053"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406005200"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5407.1535"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002030000218"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature17625"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00495-12"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2013.02.006"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2009.01.056"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2007.05.017"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00239-002-2330-4"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2021.11.024"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.12.7898-7903.2001"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34798"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40588-023-00190-w"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-143-2-331"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsle.2005.02.015"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201200228"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.3791\/63655"},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.662563"},{"key":"e_1_3_5_62_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-237"},{"key":"e_1_3_5_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks186"},{"key":"e_1_3_5_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2017.005"},{"key":"e_1_3_5_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00201-17"},{"key":"e_1_3_5_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.01.023"},{"key":"e_1_3_5_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.03.019"}],"container-title":["mSphere"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/msphere.00395-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/msphere.00395-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T13:02:44Z","timestamp":1761742964000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/msphere.00395-25"}},"subtitle":[],"editor":[{"given":"Rebecca S.","family":"Shapiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":66,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10,29]]}},"alternative-id":["10.1128\/msphere.00395-25"],"URL":"https:\/\/doi.org\/10.1128\/msphere.00395-25","relation":{},"ISSN":["2379-5042"],"issn-type":[{"value":"2379-5042","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,29]]},"assertion":[{"value":"2025-06-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00395-25"}}