{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:54:32Z","timestamp":1792205672064,"version":"4.4.0"},"reference-count":68,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F32AI178852"],"award-info":[{"award-number":["F32AI178852"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI137085"],"award-info":[{"award-number":["R01AI137085"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32AI007528"],"award-info":[{"award-number":["T32AI007528"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2025,8,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The Type II Secretion System (T2SS) of the Gram-negative pathogen\n                      <jats:italic toggle=\"yes\">Vibrio cholerae<\/jats:italic>\n                      is considered a virulence factor primarily because it facilitates the secretion of cholera toxin upon arrival of this pathogen in the human intestinal lumen, resulting in the profuse watery diarrhea associated with infection. Results from transposon mutagenesis screens suggest that the\n                      <jats:italic toggle=\"yes\">V. cholerae eps<\/jats:italic>\n                      genes that code for the T2SS are essential. The deletion of these genes impairs the secretion of the T2SS\u2019s nearly two dozen protein substrates, leading to the selection of suppressor mutations, extracytoplasmic stress, and poor growth of the mutant bacteria. Here, we explore the role of the C-terminal PDZ domain of the T2SS component EpsC, and why transposon insertions in\n                      <jats:italic toggle=\"yes\">pdz<\/jats:italic>\n                      do not affect bacterial viability unlike insertions in most other\n                      <jats:italic toggle=\"yes\">eps<\/jats:italic>\n                      genes. Our data show that the deletion of\n                      <jats:italic toggle=\"yes\">pdz<\/jats:italic>\n                      does not affect the growth of\n                      <jats:italic toggle=\"yes\">V. cholerae,<\/jats:italic>\n                      and we demonstrate via mass spectrometry that the serine protease VesB is the only known T2SS substrate fully reliant on PDZ for secretion. We confirm this finding with immuno- and enzyme assays and show that the immunoglobulin (Ig)-like fold of VesB contains PDZ-dependent secretion information that can be grafted onto \u03b2-lactamase, causing this normally periplasmic protein to be secreted in a PDZ-dependent manner. This work adds to a growing body of evidence about substrate selection by the T2SS and reinforces the view that the C-terminal domain of EpsC and its homologs are required for the secretion of only a subset of T2SS substrates within a given species.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      The T2SS is common in Gram-negative pathogens, facilitating the secretion of various toxins and enzymes; however, the mechanisms of substrate selection and secretion remain poorly understood. Here, we demonstrate that the C-terminal PDZ domain of the T2SS \u201cclamp\u201d protein EpsC is only required for secretion of VesB in\n                      <jats:italic toggle=\"yes\">V. cholerae<\/jats:italic>\n                      and that VesB\u2019s Ig-fold contains PDZ-dependent secretion information that can be functionally grafted onto a non-secreted periplasmic protein.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jb.00144-25","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T13:01:27Z","timestamp":1752498087000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["The PDZ domain of EpsC is required for extracellular secretion of VesB by the Type II secretion system in\n                    <i>Vibrio cholerae<\/i>"],"prefix":"10.1128","volume":"207","author":[{"given":"Austin","family":"Shannon","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of Michigan","place":["Ann Arbor, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Johnson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of Michigan","place":["Ann Arbor, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron S.","family":"Roberts","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of Michigan","place":["Ann Arbor, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine T.","family":"Chaton","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02k3smh20","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Cellular Biochemistry, University of Kentucky","place":["Lexington, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2182-6843","authenticated-orcid":true,"given":"Konstantin V.","family":"Korotkov","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02k3smh20","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular and Cellular Biochemistry, University of Kentucky","place":["Lexington, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6605-4720","authenticated-orcid":true,"given":"Maria","family":"Sandkvist","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, University of Michigan","place":["Ann Arbor, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00014-17"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00207-24"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2672.2006.03253.x"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003126"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(93)90520-d"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-021-00894-4"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.211078"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.6.3523-3535.2001"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(93)90543-c"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.173.14.4310-4317.1991"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.23.6735"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1991.tb02115.x"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2011.0204"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/ecosalplus.ESP-0034-2018"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2015.10.023"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14664"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01413-10"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.3.1393-1404.1999"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13704"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.05351-11"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.08.037"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002228"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/gbe\/evz023"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/1478-811X-8-8"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0968-0004(96)30044-3"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(04)00454-4"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0131142"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.03299-20"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1997.5591911.x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt654"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003800"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.01125-20"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00583-07"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00092-09"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuu001"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.13.4012-4019.1999"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1099\/mgen.0.000273"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-019-0603-6"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4594"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12744"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100305"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.525261"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.04.020"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2016.25"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.1986.tb03037.x"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins2030310"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.45.3.558-560.1984"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.24.15562"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/35020000"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.052694299"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028886"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007341"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01270-24"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.10.3129-3135.1999"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01292-13"},{"key":"e_1_3_3_57_2","first-page":"430","volume-title":"Methods in enzymology","author":"Cull MG","year":"2000","unstructured":"Cull MG, Schatz PJ. 2000. Biotinylation of proteins in vivo and in vitro using small peptide tags, p 430\u2013440. In Methods in enzymology. Elsevier."},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.8.4.921"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1990.tb02016.x"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.166.3.1083-1088.1986"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a124010"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1996.tb02650.x"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.20.7045-7055.2005"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.6.1431-1437.1998"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2013.06.013"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.70.1.610-612.2004"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01256-07"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.1.4.283"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"}],"container-title":["Journal of Bacteriology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jb.00144-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jb.00144-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T13:01:11Z","timestamp":1755781271000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jb.00144-25"}},"subtitle":[],"editor":[{"given":"Michael Y.","family":"Galperin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,8,21]]},"references-count":68,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8,21]]}},"alternative-id":["10.1128\/jb.00144-25"],"URL":"https:\/\/doi.org\/10.1128\/jb.00144-25","relation":{},"ISSN":["0021-9193","1098-5530"],"issn-type":[{"value":"0021-9193","type":"print"},{"value":"1098-5530","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,21]]},"assertion":[{"value":"2025-04-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00144-25"}}