{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T13:53:52Z","timestamp":1791554032244,"version":"4.3.4"},"reference-count":78,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","award":["R21AI157341"],"award-info":[{"award-number":["R21AI157341"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]},{"name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","award":["R01AI133409"],"award-info":[{"award-number":["R01AI133409"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2024,8,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Protein kinases are critical regulatory proteins in both prokaryotes and eukaryotes. Accordingly, protein kinases represent a common drug target for a wide range of human diseases. Therefore, understanding protein kinase function in human pathogens such as the fungus\n                      <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                      is likely to extend our knowledge of its pathobiology and identify new potential therapies. To facilitate the study of\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      protein kinases, we constructed a library of 99 non-essential protein kinase homozygous deletion mutants marked with barcodes in the widely used SN genetic background. Here, we describe the construction of this library and the characterization of the competitive fitness of the protein kinase mutants under 11 different growth and stress conditions. We also screened the library for protein kinase mutants with altered filamentation and biofilm formation, two critical virulence traits of\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      . An extensive network of protein kinases governs these virulence traits in a manner highly dependent on the specific environmental conditions. Studies on specific protein kinases revealed that (i) the cell wall integrity MAPK pathway plays a condition-dependent role in filament initiation and elongation; (ii) the hyper-osmolar glycerol MAPK pathway is required for both filamentation and biofilm formation, particularly in the setting of\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      catheter infection; and (iii) Sok1 is dispensable for filamentation in hypoxic environments at the basal level of a biofilm but is required for filamentation in normoxia. In addition to providing a new genetic resource for the community, these observations emphasize the environmentally contingent function of\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      protein kinases.\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 one of the most common causes of fungal disease in humans for which new therapies are needed. Protein kinases are key regulatory proteins and are increasingly targeted by drugs for the treatment of a wide range of diseases. Understanding protein kinase function in\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        pathogenesis may facilitate the development of new antifungal drugs. Here, we describe a new library of 99 protein kinase deletion mutants to facilitate the study of protein kinases. Furthermore, we show that the function of protein kinases in two virulence-related processes, filamentation and biofilm formation, is dependent on the specific environmental conditions.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01249-24","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T09:00:48Z","timestamp":1719824448000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Systematic analysis of the\n                    <i>Candida albicans<\/i>\n                    kinome reveals environmentally contingent protein kinase-mediated regulation of filamentation and biofilm formation\n                    <i>in vitro<\/i>\n                    and\n                    <i>in vivo<\/i>"],"prefix":"10.1128","volume":"15","author":[{"given":"Juraj","family":"Kramara","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Carver College of Medicine, University of Iowa","place":["Iowa City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7383-743X","authenticated-orcid":false,"given":"Min-Ju","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Georgia","place":["Athens, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomye L.","family":"Ollinger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Carver College of Medicine, University of Iowa","place":["Iowa City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura C.","family":"Ristow","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Carver College of Medicine, University of Iowa","place":["Iowa City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan S.","family":"Wakade","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Carver College of Medicine, University of Iowa","place":["Iowa City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6343-1500","authenticated-orcid":false,"given":"Robert","family":"Zarnowski","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Infectious Disease, University of Wisconsin","place":["Madison, USA"]},{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin","place":["Madison, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Wellington","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Carver College of Medicine, University of Iowa","place":["Iowa City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7927-9950","authenticated-orcid":false,"given":"David R.","family":"Andes","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Infectious Disease, University of Wisconsin","place":["Madison, USA"]},{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin","place":["Madison, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0868-4000","authenticated-orcid":false,"given":"Aaron G.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Georgia","place":["Athens, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6330-3365","authenticated-orcid":false,"given":"Damian J.","family":"Krysan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Carver College of Medicine, University of Iowa","place":["Iowa City, USA"]},{"name":"Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa","place":["Iowa City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2023.02.010"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2018.26"},{"key":"e_1_3_5_4_2","volume-title":"Candida and candidiasis","author":"Calderone RA","year":"2002","unstructured":"Calderone RA, ed. 2002. Candida and candidiasis. American Society of Microbiology, Washington D.C."},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2004.02.002"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000783"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.605"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004211"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.07.046"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15329-2"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14191-1"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.106145"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-3155-3_10"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.02.008"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001510"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.85114"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.5b00134"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.10.048"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000752"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010283"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.4.2.298-309.2005"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00050-17"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006405"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00165-09"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-146-11-2755"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof7090739"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10123-019-00069-1"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00805-20"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1108235"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14148"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02944-22"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof9121181"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.15698\/mic2018.11.655"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006487"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200307176"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00784.x"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.10.3058-3068.1999"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-144-2-411"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407097102"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00044-12"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.17.4753"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.17.4742"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e05-01-0073"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.2.5.1053-1060.2003"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1318690111"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002663"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.3791\/64258"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1101\/2024.02.20.581211"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/apm.13310"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2006.10.003"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02503-19"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01338-18"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2011.07626.x"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-019-0558-7"},{"key":"e_1_3_5_55_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002683"},{"key":"e_1_3_5_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01900-20"},{"key":"e_1_3_5_57_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020063"},{"key":"e_1_3_5_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00436-21"},{"key":"e_1_3_5_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03498-22"},{"key":"e_1_3_5_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00305-22"},{"key":"e_1_3_5_61_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-539-8_40"},{"key":"e_1_3_5_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00637-12"},{"key":"e_1_3_5_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107059"},{"key":"e_1_3_5_64_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10123-021-00183-z"},{"key":"e_1_3_5_65_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1010890"},{"key":"e_1_3_5_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104432"},{"key":"e_1_3_5_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00134-23"},{"key":"e_1_3_5_68_2","doi-asserted-by":"publisher","unstructured":"Wakade RS Wellington M Krysan DJ. 2024. The role of the C. albicans transcriptional repressor NRG1 during filamentation and disseminated candidiasis is strain-dependent. bioRxiv. doi:10.1101\/2023.12.15.571891","DOI":"10.1101\/2023.12.15.571891"},{"key":"e_1_3_5_69_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12275-016-5550-9"},{"key":"e_1_3_5_70_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E11-03-0205"},{"key":"e_1_3_5_71_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00011-15"},{"key":"e_1_3_5_72_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13681"},{"key":"e_1_3_5_73_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009861"},{"key":"e_1_3_5_74_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00016-15"},{"key":"e_1_3_5_75_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.19"},{"key":"e_1_3_5_76_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.6.1868-1874.1999"},{"key":"e_1_3_5_77_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006948"},{"key":"e_1_3_5_78_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01767-19"},{"key":"e_1_3_5_79_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00148-14"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.01249-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.01249-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T13:37:05Z","timestamp":1791553025000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.01249-24"}},"subtitle":[],"editor":[{"given":"Judith","family":"Berman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,8,14]]},"references-count":78,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8,14]]}},"alternative-id":["10.1128\/mbio.01249-24"],"URL":"https:\/\/doi.org\/10.1128\/mbio.01249-24","relation":{},"ISSN":["2150-7511"],"issn-type":[{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,14]]},"assertion":[{"value":"2024-04-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01249-24"}}