{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:54:53Z","timestamp":1792673693219,"version":"4.5.0"},"reference-count":68,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI047141"],"award-info":[{"award-number":["R01 AI047141"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AI065555"],"award-info":[{"award-number":["R21 AI065555"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI084400"],"award-info":[{"award-number":["R01 AI084400"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["U19 AI31496"],"award-info":[{"award-number":["U19 AI31496"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI097312"],"award-info":[{"award-number":["R01 AI097312"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AI110889"],"award-info":[{"award-number":["R21 AI110889"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI097312-S1"],"award-info":[{"award-number":["R01 AI097312-S1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005430","name":"American Society for Microbiology","doi-asserted-by":"publisher","award":["Robert D. Watkins fellowship"],"award-info":[{"award-number":["Robert D. Watkins fellowship"]}],"id":[{"id":"10.13039\/100005430","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:named-content content-type=\"genus-species\">Neisseria gonorrhoeae<\/jats:named-content>successfully overcomes host strategies to limit essential nutrients, termed nutritional immunity, by production of TonB-dependent transporters (TdTs)\u2014outer membrane proteins that facilitate nutrient transport in an energy-dependent manner. Four gonococcal TdTs facilitate utilization of iron or iron chelates from host-derived proteins, including transferrin (TbpA), lactoferrin (LbpA), and hemoglobin (HpuB), in addition to xenosiderophores from other bacteria (FetA). The roles of the remaining four uncharacterized TdTs (TdfF, TdfG, TdfH, and TdfJ) remain elusive. Regulatory data demonstrating that production of gonococcal TdfH and TdfJ are unresponsive to or upregulated under iron-replete conditions led us to evaluate the role of these TdTs in the acquisition of nutrients other than iron. In this study, we found that production of gonococcal TdfH is both Zn and Zur repressed. We also found that TdfH confers resistance to calprotectin, an immune effector protein highly produced in neutrophils that has antimicrobial activity due to its ability to sequester Zn and Mn. We found that TdfH directly binds calprotectin, which enables gonococcal Zn accumulation in a TdfH-dependent manner and enhances bacterial survival after exposure to neutrophil extracellular traps (NETs). These studies highlight Zn sequestration by calprotectin as a key functional arm of NET-mediated killing of gonococci. We demonstrate for the first time that<jats:named-content content-type=\"genus-species\">N. gonorrhoeae<\/jats:named-content>exploits this host strategy in a novel defense mechanism, in which TdfH production hijacks and directly utilizes the host protein calprotectin as a zinc source and thereby evades nutritional immunity.<\/jats:p>","DOI":"10.1128\/iai.00319-16","type":"journal-article","created":{"date-parts":[[2016,8,2]],"date-time":"2016-08-02T03:05:13Z","timestamp":1470107113000},"page":"2982-2994","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":62,"title":["Neisseria gonorrhoeae Evades Calprotectin-Mediated Nutritional Immunity and Survives Neutrophil Extracellular Traps by Production of TdfH"],"prefix":"10.1128","volume":"84","author":[{"given":"Sophonie","family":"Jean","sequence":"first","affiliation":[{"name":"Integrative Life Sciences Program, Department of Biology, Virginia Commonwealth University, Richmond, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Juneau","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison K.","family":"Criss","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia N.","family":"Cornelissen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Sexually transmitted disease surveillance 2014","author":"Centers for Disease Control and Prevention","year":"2015","unstructured":"Centers for Disease Control and Prevention. 2015. Sexually transmitted disease surveillance 2014. Centers for Disease Control and Prevention, Atlanta, GA."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/OLQ.0b013e318285c6d2"},{"key":"e_1_3_2_4_2","first-page":"332","article-title":"Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections","volume":"56","author":"Centers for Disease Control and Prevention","year":"2007","unstructured":"Centers for Disease Control and Prevention. 2007. Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep 56:332\u2013336.","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2011.06215.x"},{"key":"e_1_3_2_6_2","first-page":"590","article-title":"Update to CDC's sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections","volume":"61","author":"Centers for Disease Control and Prevention","year":"2012","unstructured":"Centers for Disease Control and Prevention. 2012. Update to CDC's sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb Mortal Wkly Rep 61:590\u2013594.","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05760-11"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00325-11"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00124"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00052"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.08.067"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.112408.134247"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1139\/O10-141"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00117"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.00710.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00077"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2713"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20122220"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12117"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2008.01205.x"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2009.01308.x"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv031"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2836"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2009.11.008"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/pr0603699"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)89506-4"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1152449"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000639"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004450"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003068"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2011.01.021"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2011.07.004"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.01.017"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/174.6.1369"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000969"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003733"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8996"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.85.6.1274-1279.1963"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.47.2.388-394.1985"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00807-10"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1998.01089.x"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05429.x"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00171-13"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/227680a0"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-147-5-1277"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.3.1612-1620.2006"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja307974e"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01007-07"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401433200"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00363-09"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220341110"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011835"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1992.tb05535.x"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.11.3572-3579.1997"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.3.805-812.1997"},{"key":"e_1_3_2_59_2","doi-asserted-by":"crossref","first-page":"6291","DOI":"10.4049\/jimmunol.151.11.6291","article-title":"In vitro candidastatic properties of the human neutrophil calprotectin complex","volume":"151","author":"Murthy AR","year":"1993","unstructured":"Murthy AR, Lehrer RI, Harwig SS, Miyasaki KT. 1993. In vitro candidastatic properties of the human neutrophil calprotectin complex. J Immunol 151:6291\u20136301.","journal-title":"J Immunol"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12238"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5MT00017C"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.14.4865-4874.2005"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01091-12"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05079.x"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01725-07"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12288"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002987"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004593"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.120.3.1293-1299.1974"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.32.2.641-648.1981"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00319-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.00319-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T12:49:14Z","timestamp":1692449354000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.00319-16"}},"subtitle":[],"editor":[{"given":"S. M.","family":"Payne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,10]]},"references-count":68,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1128\/IAI.00319-16"],"URL":"https:\/\/doi.org\/10.1128\/iai.00319-16","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10]]},"assertion":[{"value":"2016-04-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-07-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-09-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}