{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:25:21Z","timestamp":1792185921408,"version":"4.4.0"},"reference-count":139,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI144182, R01AI127793, R01AI125421"],"award-info":[{"award-number":["U19AI144182, R01AI127793, R01AI125421"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Transition metals are essential for metalloprotein function among all domains of life. Humans utilize nutritional immunity to limit bacterial infections, employing metalloproteins such as hemoglobin, transferrin, and lactoferrin across a variety of physiological niches to sequester iron from invading bacteria. Consequently, some bacteria have evolved mechanisms to pirate the sequestered metals and thrive in these metal-restricted environments. <jats:italic>Neisseria gonorrhoeae<\/jats:italic>, the causative agent of the sexually transmitted infection gonorrhea, causes devastating disease worldwide and is an example of a bacterium capable of circumventing human nutritional immunity. <jats:italic>Via<\/jats:italic> production of specific outer-membrane metallotransporters, <jats:italic>N. gonorrhoeae<\/jats:italic> is capable of extracting iron directly from human innate immunity metalloproteins. This review focuses on the function and expression of each metalloprotein at gonococcal infection sites, as well as what is known about how the gonococcus accesses bound iron.<\/jats:p>","DOI":"10.3389\/fcimb.2022.1017348","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T06:25:50Z","timestamp":1663223150000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Stealthy microbes: How Neisseria gonorrhoeae hijacks bulwarked iron during infection"],"prefix":"10.3389","volume":"12","author":[{"given":"Julie Lynn","family":"Stoudenmire","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley Nicole","family":"Greenawalt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia Nau","family":"Cornelissen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4281","DOI":"10.1128\/IAI.73.7.4281-4287.2005","article-title":"The gonococcal fur-regulated tbpA and tbpB genes are expressed during natural mucosal gonococcal infection","volume":"73","author":"Agarwal","year":"2005","journal-title":"Infect. Immun."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1016\/S0021-9258(19)62337-9","article-title":"Stoichiometric and site characteristics of the binding of iron to human transferrin","volume":"253","author":"Aisen","year":"1978","journal-title":"J. Biol. Chem."},{"key":"B3","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1139\/o2012-013","article-title":"Lactoferrin: An alternative view of its role in human biological fluids","volume":"90","author":"Alexander","year":"2012","journal-title":"Biochem. Cell Biol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1046\/j.1365-2958.2003.03496.x","article-title":"Opposing selective forces for expression of the gonococcal lactoferrin receptor","volume":"48","author":"Anderson","year":"2003","journal-title":"Mol. Microbiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1086\/324564","article-title":"Selection for expression of the gonococcal hemoglobin receptor during menses","volume":"184","author":"Anderson","year":"2001","journal-title":"J. Infect. Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3162","DOI":"10.1128\/jb.176.11.3162-3170.1994","article-title":"Gonococcal transferrin-binding protein 2 facilitates but is not essential for transferrin utilization","volume":"176","author":"Anderson","year":"1994","journal-title":"J. Bacteriol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1039\/c8mt00146d","article-title":"The human iron-proteome","volume":"10","author":"Andreini","year":"2018","journal-title":"Metallomics"},{"key":"B8","doi-asserted-by":"crossref","DOI":"10.1002\/9781119252863.ch13","volume-title":"The molecular basis of iron metabolism","author":"Andrews","year":"2019"},{"key":"B9","doi-asserted-by":"publisher","first-page":"4977","DOI":"10.1128\/IAI.00613-10","article-title":"Overcoming the heme paradox: Heme toxicity and tolerance in bacterial pathogens","volume":"78","author":"Anzaldi","year":"2010","journal-title":"Infect. Immun."},{"key":"B10","doi-asserted-by":"publisher","first-page":"4129","DOI":"10.1182\/blood-2011-04-351957","article-title":"Hepcidin regulation by innate immune and infectious stimuli","volume":"118","author":"Armitage","year":"2011","journal-title":"Blood"},{"key":"B11","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1023\/B:BIOM.0000027694.40260.70","article-title":"Lactoferrin and iron: Structural and dynamic aspects of binding and release","volume":"17","author":"Baker","year":"2004","journal-title":"Biometals"},{"key":"B12","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1139\/o01-153","article-title":"Lactoferrin and transferrin: Functional variations on a common structural framework","volume":"80","author":"Baker","year":"2002","journal-title":"Biochem. Cell Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/0079-6107(76)90024-9","article-title":"Structure and function of haemoglobin","volume":"29","author":"Baldwin","year":"1975","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1038\/nchembio.402","article-title":"Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex","volume":"6","author":"Bao","year":"2010","journal-title":"Nat. Chem. Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1136\/sextrans-2013-051119","article-title":"Changing patterns of disseminated gonococcal infection in France: cross-sectional data 2009-2011","volume":"89","author":"Belkacem","year":"2013","journal-title":"Sex Transm. Infect."},{"key":"B16","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1128\/IAI.67.1.455-459.1999","article-title":"Identification and functional characterization of the Neisseria gonorrhoeae lbpB gene product","volume":"67","author":"Biswas","year":"1999","journal-title":"Infect. Immun."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2958","DOI":"10.1128\/iai.63.8.2958-2967.1995","article-title":"Characterization of lbpA, the structural gene for a lactoferrin receptor in Neisseria gonorrhoeae","volume":"63","author":"Biswas","year":"1995","journal-title":"Infect. Immun."},{"key":"B18","doi-asserted-by":"publisher","first-page":"5225","DOI":"10.1128\/jb.172.9.5225-5235.1990","article-title":"Genetic evidence that Neisseria gonorrhoeae produces specific receptors for transferrin and lactoferrin","volume":"172","author":"Blanton","year":"1990","journal-title":"J. Bacteriol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1046\/j.1462-5822.2000.00042.x","article-title":"Alteration of epithelial cell transferrin-iron homeostasis by Neisseria meningitidis and Neisseria gonorrhoeae","volume":"2","author":"Bonnah","year":"2000","journal-title":"Cell Microbiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1111\/j.1462-5822.2004.00376.x","article-title":"Expression of epithelial cell iron-related genes upon infection by Neisseria meningitidis","volume":"6","author":"Bonnah","year":"2004","journal-title":"Cell Microbiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"3080","DOI":"10.1128\/JB.180.12.3080-3090.1998","article-title":"Preparation and characterization of Neisseria meningitidis mutants deficient in production of the human lactoferrin-binding proteins LbpA and LbpB","volume":"180","author":"Bonnah","year":"1998","journal-title":"J. Bacteriol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1097\/00075197-199911000-00013","article-title":"Benefits and dangers of iron during infection","volume":"2","author":"Brock","year":"1999","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"B23","first-page":"550","article-title":"Tear lactoferrin: A bacteriostatic and complexing protein","volume":"13","author":"Broekhuyse","year":"1974","journal-title":"Invest. Ophthalmol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2895","DOI":"10.1128\/JB.181.9.2895-2901.1999","article-title":"Ferric enterobactin binding and utilization by Neisseria gonorrhoeae","volume":"181","author":"Carson","year":"1999","journal-title":"J. Bacteriol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1172\/JCI101690","article-title":"The anemia of infection, hypoferremia, hypercupremia, and alterations in porphyrin metabolism in patients","volume":"25","author":"Cartwright","year":"1946","journal-title":"J. Clin. Invest."},{"key":"B26","doi-asserted-by":"publisher","first-page":"4438","DOI":"10.1128\/IAI.00762-15","article-title":"Beyond the crystal structure: Insight into the function and vaccine potential of TbpA expressed by Neisseria gonorrhoeae","volume":"83","author":"Cash","year":"2015","journal-title":"Infect. Immun."},{"key":"B27","article-title":"Incidence, prevalence and cost of sexually transmitted infections in the united states","year":"2021"},{"key":"B28","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.bbcan.2012.03.008","article-title":"The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer","volume":"1826","author":"Chakraborty","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"B29","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1007\/s10534-018-0105-7","article-title":"Are lactoferrin receptors in gram-negative bacteria viable vaccine targets","volume":"31","author":"Chan","year":"2018","journal-title":"Biometals"},{"key":"B30","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1128\/IAI.66.3.987-993.1998","article-title":"Phase variation of hemoglobin utilization in Neisseria gonorrhoeae","volume":"66","author":"Chen","year":"1998","journal-title":"Infect. Immun."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1016\/S0002-9378(87)80274-0","article-title":"Preliminary observations on lactoferrin secretion in human vaginal mucus: Variation during the menstrual cycle, evidence of hormonal regulation, and implications for infection with Neisseria gonorrhoeae","volume":"157","author":"Cohen","year":"1987","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"287","DOI":"10.2217\/17460913.3.3.287","article-title":"Identification and characterization of gonococcal iron transport systems as potential vaccine antigens","volume":"3","author":"Cornelissen","year":"2008","journal-title":"Future Microbiol."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftx112","article-title":"Subversion of nutritional immunity by the pathogenic Neisseriae","volume":"76","author":"Cornelissen","year":"2018","journal-title":"Pathog. Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"4725","DOI":"10.1128\/IAI.68.8.4725-4735.2000","article-title":"Antigenic and sequence diversity in gonococcal transferrin-binding protein a","volume":"68","author":"Cornelissen","year":"2000","journal-title":"Infect. Immun."},{"key":"B35","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1128\/iai.65.2.822-828.1997","article-title":"Characterization of the diversity and the transferrin-binding domain of gonococcal transferrin-binding protein 2","volume":"65","author":"Cornelissen","year":"1997","journal-title":"Infect. Immun."},{"key":"B36","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1046\/j.1365-2958.1997.5381914.x","article-title":"Energy-dependent changes in the gonococcal transferrin receptor","volume":"26","author":"Cornelissen","year":"1997","journal-title":"Mol. Microbiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"5788","DOI":"10.1128\/jb.174.18.5788-5797.1992","article-title":"Gonococcal transferrin-binding protein 1 is required for transferrin utilization and is homologous to TonB-dependent outer membrane receptors","volume":"174","author":"Cornelissen","year":"1992","journal-title":"J. Bacteriol."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00117","article-title":"TonB-dependent transporters expressed by Neisseria gonorrhoeae","volume":"2","author":"Cornelissen","year":"2011","journal-title":"Front. Microbiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1046\/j.1365-2958.1998.00710.x","article-title":"The transferrin receptor expressed by gonococcal strain FA1090 is required for the experimental infection of human male volunteers","volume":"27","author":"Cornelissen","year":"1998","journal-title":"Mol. Microbiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1128\/jb.178.5.1437-1444.1996","article-title":"Binding and surface exposure characteristics of the gonococcal transferrin receptor are dependent on both transferrin-binding proteins","volume":"178","author":"Cornelissen","year":"1996","journal-title":"J. Bacteriol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"13524","DOI":"10.1074\/jbc.R111.311829","article-title":"Mammalian siderophores, siderophore-binding lipocalins, and the labile iron pool","volume":"287","author":"Correnti","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B42","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1038\/nrmicro2713","article-title":"A bacterial siren song: Intimate interactions between Neisseria and neutrophils","volume":"10","author":"Criss","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.15585\/mmwr.mm6950a6","article-title":"Update to CDC's treatment guidelines for gonococcal infection, 2020","volume":"69","author":"Cyr","year":"2020","journal-title":"Morb. Mortality Weekly Rep"},{"key":"B44","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.yexcr.2005.07.002","article-title":"A physiological model to study iron recycling in macrophages","volume":"310","author":"Delaby","year":"2005","journal-title":"Exp. Cell Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1016\/j.cell.2010.04.040","article-title":"A mammalian siderophore synthesized by an enzyme with a bacterial homolog involved in enterobactin production","volume":"141","author":"Devireddy","year":"2010","journal-title":"Cell"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.3906\/kim-2102-25","article-title":"Structural rearrangement of Neisseria meningitidis transferrin binding protein a (TbpA) prior to human transferrin protein (hTf) binding","volume":"45","author":"Duran","year":"2021","journal-title":"Turkish J. Chem."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1093\/jac\/dkaa559","article-title":"What\u2019s left in the cupboard? Older antimicrobials for treating gonorrhoea","volume":"76","author":"Fifer","year":"2021","journal-title":"J. Antimicrob. Chemother"},{"key":"B48","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.biochi.2008.07.007","article-title":"Role of lactoferrin in the tear film","volume":"91","author":"Flanagan","year":"2009","journal-title":"Biochimie"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1128\/IAI.02572-14","article-title":"Nonbinding site-directed mutants of transferrin binding protein b exhibit enhanced immunogenicity and protective capabilities","volume":"83","author":"Frandoloso","year":"2015","journal-title":"Infect. Immun."},{"key":"B50","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1053\/j.seminhematol.2009.06.001","article-title":"Iron sequestration and anemia of inflammation","volume":"46","author":"Ganz","year":"2009","journal-title":"Semin. Hematol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1038\/nri3863","article-title":"Iron homeostasis in host defence and inflammation","volume":"15","author":"Ganz","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1016\/S1097-2765(02)00708-6","article-title":"The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition","volume":"10","author":"Goetz","year":"2002","journal-title":"Mol. Cell"},{"key":"B53","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1159\/000494627","article-title":"The iron tug-of-War between bacterial siderophores and innate immunity","volume":"11","author":"Golonka","year":"2019","journal-title":"J. Innate Immun."},{"key":"B54","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/0966-842X(96)10025-1","article-title":"Bacterial transferrin and lactoferrin receptors","volume":"4","author":"Gray-Owen","year":"1996","journal-title":"Trends Microbiol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1146\/annurev.mi.48.100194.003523","article-title":"Microbial iron transport","volume":"48","author":"Guerinot","year":"1994","journal-title":"Annu. Rev. Microbiol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1111\/j.1365-2958.2006.05429.x","article-title":"Neisseria gonorrhoeae requires expression of TonB and the putative transporter TdfF to replicate within cervical epithelial cells","volume":"62","author":"Hagen","year":"2006","journal-title":"Mol. Microbiol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.bbapap.2017.01.006","article-title":"Diverse structural approaches to haem appropriation by pathogenic bacteria","volume":"1865","author":"Hare","year":"2017","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"B58","doi-asserted-by":"publisher","first-page":"4764","DOI":"10.1128\/IAI.05806-11","article-title":"The iron-repressed, AraC-like regulator MpeR activates expression of fetA in Neisseria gonorrhoeae","volume":"79","author":"Hollander","year":"2011","journal-title":"Infect. Immun."},{"key":"B59","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/nrmicro2836","article-title":"Nutritional immunity: transition metals at the pathogen-host interface","volume":"10","author":"Hood","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1111\/j.1365-2958.1993.tb01657.x","article-title":"Preparation and analysis of isogenic mutants in the transferrin receptor protein genes, tbpA and tbpB, from Neisseria meningitidis","volume":"8","author":"Irwin","year":"1993","journal-title":"Mol. Microbiol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1128\/JB.00741-09","article-title":"Transcriptional and functional analysis of the Neisseria gonorrhoeae fur regulon","volume":"192","author":"Jackson","year":"2010","journal-title":"J. Bacteriol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1128\/IAI.00319-16","article-title":"Neisseria gonorrhoeae evades calprotectin-mediated nutritional immunity and survives neutrophil extracellular traps by production of TdfH","volume":"84","author":"Jean","year":"2016","journal-title":"Infect. Immun."},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00949-20","article-title":"Molecular insight into TdfH-mediated zinc piracy from human calprotectin by Neisseria gonorrhoeae","volume":"11","author":"Kammerman","year":"2020","journal-title":"mBio"},{"key":"B64","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1002\/2211-5463.12103","article-title":"Differential heme release from various hemoglobin redox states and the upregulation of cellular heme oxygenase-1","volume":"6","author":"Kassa","year":"2016","journal-title":"FEBS Open Bio"},{"key":"B65","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1016\/j.ijid.2007.04.007","article-title":"Association of hemochromatosis with infectious diseases: Expanding spectrum","volume":"11","author":"Khan","year":"2007","journal-title":"Int. J. Infect. Dis."},{"key":"B66","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/S0167-4838(00)00152-7","article-title":"Human neutrophil gelatinase-associated lipocalin and homologous proteins in rat and mouse","volume":"1482","author":"Kjeldsen","year":"2000","journal-title":"Biochim. Biophys. Acta"},{"key":"B67","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1007\/bf00770247","article-title":"Mechanisms of TonB-catalyzed iron transport through the enteric bacterial cell envelope","volume":"25","author":"Klebba","year":"1993","journal-title":"J. Bioenerg. Biomembr."},{"key":"B68","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1038\/35051594","article-title":"Identification of the haemoglobin scavenger receptor","volume":"409","author":"Kristiansen","year":"2001","journal-title":"Nature"},{"key":"B69","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1023\/A:1006935908960","article-title":"Lactoferrin protects gut mucosal integrity during endotoxemia induced by lipopolysaccharide in mice","volume":"24","author":"Kruzel","year":"2000","journal-title":"Inflammation"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24071323","article-title":"Lactoferrin in aseptic and septic inflammation","volume":"24","author":"Lepanto","year":"2019","journal-title":"Molecules"},{"key":"B71","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1046\/j.1365-2958.1999.01409.x","article-title":"Phase variation of HpuAB and HmbR, two distinct haemoglobin receptors of Neisseria meningitidis DNM2","volume":"32","author":"Lewis","year":"1999","journal-title":"Mol. Microbiol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1046\/j.1365-2958.1997.2501619.x","article-title":"Molecular characterization of hpuAB, the haemoglobin-haptoglobin-utilization operon of Neisseria meningitidis","volume":"23","author":"Lewis","year":"1997","journal-title":"Mol. Microbiol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1203\/00006450-198506000-00012","article-title":"Sequential changes in the antimicrobial protein concentrations in human milk during lactation and its relevance to banked human milk","volume":"19","author":"Lewis-Jones","year":"1985","journal-title":"Pediatr. Res."},{"key":"B74","doi-asserted-by":"publisher","first-page":"6043","DOI":"10.1128\/JB.180.22.6043-6047.1998","article-title":"Transport of intact porphyrin by HpuAB, the hemoglobin-haptoglobin utilization system of Neisseria meningitidis","volume":"180","author":"Lewis","year":"1998","journal-title":"J. Bacteriol."},{"key":"B75","volume-title":"Gonococcal arthritis","author":"Li","year":"2020"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00052","article-title":"New concepts in immunity to Neisseria gonorrhoeae: Innate responses and suppression of adaptive immunity favor the pathogen, not the host","volume":"2","author":"Liu","year":"2011","journal-title":"Front. Microbiol."},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011835","article-title":"Genome sequencing reveals widespread virulence gene exchange among human Neisseria species","volume":"5","author":"Marri","year":"2010","journal-title":"PloS One"},{"key":"B78","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.vetimm.2011.07.002","article-title":"Acute phase protein concentrations in colostrum-deprived pigs immunized with subunit and commercial vaccines against gl\u00e4sser\u2019s disease","volume":"144","author":"Martinez-Martinez","year":"2011","journal-title":"Vet. Immunol. Immunopathol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.vetimm.2016.07.011","article-title":"A vaccine based on a mutant transferrin binding protein b of Haemophilus parasuis induces a strong T-helper 2 response and bacterial clearance after experimental infection","volume":"179","author":"Mart\u00ednez-Mart\u00ednez","year":"2016","journal-title":"Vet. Immunol. Immunopathol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.cimid.2016.08.005","article-title":"Molecular analysis of lungs from pigs immunized with a mutant transferrin binding protein b-based vaccine and challenged with Haemophilus parasuis","volume":"48","author":"Martinez-Martinez","year":"2016","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"B81","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1111\/j.1432-1033.1968.tb00484.x","article-title":"Metal-combining properties of human lactoferrin (red milk protein)","volume":"6","author":"Masson","year":"1968","journal-title":"Eur. J. Biochem."},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007937","article-title":"The novel interaction between Neisseria gonorrhoeae TdfJ and human S100A7 allows gonococci to subvert host zinc restriction","volume":"15","author":"Maurakis","year":"2019","journal-title":"PloS Pathog."},{"key":"B83","article-title":"Iron overload","author":"McDowell","year":"2022","journal-title":"StatPearls"},{"key":"B84","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1128\/iai.33.2.555-564.1981","article-title":"Ability of Neisseria gonorrhoeae, Neisseria meningitidis, and commensal Neisseria species to obtain iron from transferrin and iron compounds","volume":"33","author":"Mickelsen","year":"1981","journal-title":"Infect. Immun."},{"key":"B85","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1128\/MMBR.00012-07","article-title":"Siderophore-based iron acquisition and pathogen control","volume":"71","author":"Miethke","year":"2007","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00152","article-title":"Iron at the interface of immunity and infection","volume":"5","author":"Nairz","year":"2014","journal-title":"Front. Pharmacol."},{"key":"B87","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1038\/nchembio.1891","article-title":"Human calprotectin is an iron-sequestering host-defense protein","volume":"11","author":"Nakashige","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1373\/clinchem.2005.055657","article-title":"Serum free hemoglobin concentrations in healthy individuals are related to haptoglobin type","volume":"51","author":"Na","year":"2005","journal-title":"Clin. Chem."},{"key":"B89","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1172\/JCI200420945","article-title":"IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin","volume":"113","author":"Nemeth","year":"2004","journal-title":"J. Clin. Invest."},{"key":"B90","doi-asserted-by":"publisher","first-page":"2090","DOI":"10.1126\/science.1104742","article-title":"Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization","volume":"306","author":"Nemeth","year":"2004","journal-title":"Science"},{"key":"B91","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.sbi.2014.02.007","article-title":"Structural insights into the transport of small molecules across membranes","volume":"27","author":"Noinaj","year":"2014","journal-title":"Curr. Opin. Struct. Biol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"vii","DOI":"10.1016\/j.sbi.2018.10.005","article-title":"Editorial overview: Membranes and their embedded molecular machines","volume":"51","author":"Noinaj","year":"2018","journal-title":"Curr. Opin. Struct. Biol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1111\/mmi.12002","article-title":"The transferrin-iron import system from pathogenic Neisseria species","volume":"86","author":"Noinaj","year":"2012","journal-title":"Mol. Microbiol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.jsb.2013.02.009","article-title":"Structural insight into the lactoferrin receptors from pathogenic Neisseria","volume":"184","author":"Noinaj","year":"2013","journal-title":"J. Struct. Biol."},{"key":"B95","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/nature10823","article-title":"Structural basis for iron piracy by pathogenic Neisseria","volume":"483","author":"Noinaj","year":"2012","journal-title":"Nature"},{"key":"B96","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1146\/annurev.micro.112408.134247","article-title":"TonB-dependent transporters: regulation, structure, and function","volume":"64","author":"Noinaj","year":"2010","journal-title":"Annu. Rev. Microbiol."},{"key":"B97","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/nrmicro.2016.191","article-title":"The beta-barrel assembly machinery in motion","volume":"15","author":"Noinaj","year":"2017","journal-title":"Nat. Rev. Microbiol."},{"key":"B98","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.1128\/IAI.00020-08","article-title":"Identification of TbpA residues required for transferrin-iron utilization by Neisseria gonorrhoeae","volume":"76","author":"Noto","year":"2008","journal-title":"Infect. Immun."},{"key":"B99","first-page":"159","article-title":"Plasma elastase alpha 1-antitrypsin and lactoferrin in sepsis: evidence for neutrophils as mediators in fatal sepsis","volume":"119","author":"Nuijens","year":"1992","journal-title":"J. Lab. Clin. Med."},{"key":"B100","doi-asserted-by":"publisher","first-page":"3538","DOI":"10.1128\/AAC.00325-11","article-title":"Is Neisseria gonorrhoeae initiating a future era of untreatable gonorrhea?: Detailed characterization of the first strain with high-level resistance to ceftriaxone","volume":"55","author":"Ohnishi","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"B101","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.ebiom.2016.07.012","article-title":"Lactoferrin suppresses neutrophil extracellular traps release in inflammation","volume":"10","author":"Okubo","year":"2016","journal-title":"EBioMedicine"},{"key":"B102","doi-asserted-by":"publisher","first-page":"S529","DOI":"10.1093\/cid\/ciz825","article-title":"The role of iron and siderophores in infection, and the development of siderophore antibiotics","volume":"69","author":"Page","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"B103","doi-asserted-by":"publisher","first-page":"5705","DOI":"10.1021\/bi300752r","article-title":"Mechanisms of mammalian iron homeostasis","volume":"51","author":"Pantopoulos","year":"2012","journal-title":"Biochemistry"},{"key":"B104","doi-asserted-by":"publisher","first-page":"1764","DOI":"10.1128\/jb.176.6.1764-1766.1994","article-title":"Identification of the iroA gene product of Neisseria meningitidis as a lactoferrin receptor","volume":"176","author":"Pettersson","year":"1994","journal-title":"J. Bacteriol."},{"key":"B105","first-page":"169","article-title":"Asymptomatic gonorrhea in the male","volume":"110","author":"Portnoy","year":"1974","journal-title":"Can. Med. Assoc. J."},{"key":"B106","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1007\/bf00770246","article-title":"TonB protein and energy transduction between membranes","volume":"25","author":"Postle","year":"1993","journal-title":"J. Bioenerg. Biomembr."},{"key":"B107","doi-asserted-by":"publisher","first-page":"883","DOI":"10.3109\/02713683.2015.1075220","article-title":"Lactoferrin expression in human and murine ocular tissue","volume":"41","author":"Rageh","year":"2016","journal-title":"Curr. Eye Res."},{"key":"B108","doi-asserted-by":"publisher","first-page":"3584","DOI":"10.1073\/pnas.0630018100","article-title":"Enterobactin: An archetype for microbial iron transport","volume":"100","author":"Raymond","year":"2003","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B109","doi-asserted-by":"publisher","first-page":"3461","DOI":"10.1128\/IAI.72.6.3461-3470.2004","article-title":"Role of transferrin receptor from a Neisseria meningitidis tbpB isotype II strain in human transferrin binding and virulence","volume":"72","author":"Renauld-Mong\u00e9nie","year":"2004","journal-title":"Infect. Immun."},{"key":"B110","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1006\/mpat.1998.0226","article-title":"Discrimination between apo and iron-loaded forms of transferrin by transferrin binding protein b and its n-terminal subfragment","volume":"25","author":"Retzer","year":"1998","journal-title":"Microb. Pathog."},{"key":"B111","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1016\/j.idc.2005.07.003","article-title":"Gonococcal arthritis (disseminated gonococcal infection)","volume":"19","author":"Rice","year":"2005","journal-title":"Infect. Dis. Clin. North Am."},{"key":"B112","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1146\/annurev-micro-090816-093530","article-title":"Neisseria gonorrhoeae: Drug resistance, mouse models, and vaccine development","volume":"71","author":"Rice","year":"2017","journal-title":"Annu. Rev. Microbiol."},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.2741\/1133","article-title":"Mechanisms of iron acquisition by the human pathogen Neisseria meningitidis and Neisseria gonorrhoeae","volume":"33","author":"Rohde","year":"2003","journal-title":"Front. Biosci."},{"key":"B114","doi-asserted-by":"publisher","first-page":"2494","DOI":"10.1128\/IAI.72.5.2494-2506.2004","article-title":"Analysis of haptoglobin and hemoglobin-haptoglobin interactions with the Neisseria meningitidis TonB-dependent receptor HpuAB by flow cytometry","volume":"72","author":"Rohde","year":"2004","journal-title":"Infect. Immun."},{"key":"B115","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1046\/j.1365-2958.2002.02745.x","article-title":"Interactions of haemoglobin with the Neisseria meningitidis receptor HpuAB: The role of TonB and an intact proton motive force","volume":"43","author":"Rohde","year":"2002","journal-title":"Mol. Microbiol."},{"key":"B116","doi-asserted-by":"publisher","first-page":"1581s","DOI":"10.3945\/ajcn.117.155838","article-title":"Impact of chronic and acute inflammation on extra- and intracellular iron homeostasis","volume":"106","author":"Ross","year":"2017","journal-title":"Am. J. Clin. Nutr."},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02417","article-title":"Progress toward a gonococcal vaccine: The way forward","volume":"10","author":"Russell","year":"2019","journal-title":"Front. Immunol."},{"key":"B118","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1097\/00007435-200110000-00001","article-title":"Experimental gonococcal urethritis and reinfection with homologous gonococci in male volunteers","volume":"28","author":"Schmidt","year":"2001","journal-title":"Sex Transm. Dis."},{"key":"B119","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1128\/iai.56.5.1144-1149.1988","article-title":"Identification and characterization of the human lactoferrin-binding protein from Neisseria meningitidis","volume":"56","author":"Schryvers","year":"1988","journal-title":"Infect. Immun."},{"key":"B120","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1046\/j.1365-2958.1999.01411.x","article-title":"Iron acquisition systems in the pathogenic Neisseria","volume":"32","author":"Schryvers","year":"1999","journal-title":"Mol. Microbiol."},{"key":"B121","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.cbpa.2012.11.014","article-title":"Siderocalins: Siderophore binding proteins evolved for primary pathogen host defense","volume":"17","author":"Sia","year":"2013","journal-title":"Curr. Opin. Chem. Biol."},{"key":"B122","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/1471-2164-7-128","article-title":"The majority of genes in the pathogenic Neisseria species are present in non-pathogenic Neisseria lactamica, including those designated as \u2018virulence genes\u2019","volume":"7","author":"Snyder","year":"2006","journal-title":"BMC Genomics"},{"key":"B123","volume-title":"Gonorrhea","author":"Springer","year":"2020"},{"key":"B124","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1128\/IAI.00807-10","article-title":"The fbpABC operon is required for ton-independent utilization of xenosiderophores by Neisseria gonorrhoeae strain FA19","volume":"79","author":"Strange","year":"2011","journal-title":"Infect. Immun."},{"key":"B125","doi-asserted-by":"publisher","first-page":"3132","DOI":"10.1128\/iai.56.12.3132-3138.1988","article-title":"Loss of transferrin receptor activity in Neisseria meningitidis correlates with inability to use transferrin as an iron source","volume":"56","author":"Tsai","year":"1988","journal-title":"Infect. Immun."},{"key":"B126","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1099\/00221287-147-5-1277","article-title":"Neisserial TonB-dependent outer-membrane proteins: Detection, regulation and distribution of three putative candidates identified from the genome sequences","volume":"147","author":"Turner","year":"2001","journal-title":"Microbiol. (Reading)"},{"key":"B127","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/s41572-019-0128-6","article-title":"Gonorrhoea","volume":"5","author":"Unemo","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000639","article-title":"Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans","volume":"5","author":"Urban","year":"2009","journal-title":"PloS Pathog."},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00376","article-title":"Role of lactobacilli and lactoferrin in the mucosal cervicovaginal defense","volume":"9","author":"Valenti","year":"2018","journal-title":"Front. Immunol."},{"key":"B130","doi-asserted-by":"publisher","first-page":"197","DOI":"10.2147\/ijwh.S13427","article-title":"Gonorrhea infection in women: Prevalence, effects, screening, and management","volume":"3","author":"Walker","year":"2011","journal-title":"Int. J. Womens Health"},{"key":"B131","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1146\/annurev.micro.58.030603.123811","article-title":"Bacterial iron sources: from siderophores to hemophores","volume":"58","author":"Wandersman","year":"2004","journal-title":"Annu. Rev. Microbiol."},{"key":"B132","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1001\/jama.1975.03240130021018","article-title":"Nutritional immunity. host\u2019s attempt to withold iron from microbial invaders","volume":"231","author":"Weinberg","year":"1975","journal-title":"Jama"},{"key":"B133","doi-asserted-by":"publisher","first-page":"S12","DOI":"10.1046\/j.1523-1755.1999.055Suppl.69012.x","article-title":"Iron and anemia of chronic disease","volume":"69","author":"Weiss","year":"1999","journal-title":"Kidney Int. Suppl."},{"key":"B134","doi-asserted-by":"publisher","first-page":"3414","DOI":"10.1128\/jb.169.8.3414-3421.1987","article-title":"Aerobactin utilization by Neisseria gonorrhoeae and cloning of a genomic DNA fragment that complements Escherichia coli fhuB mutations","volume":"169","author":"West","year":"1987","journal-title":"J. Bacteriol."},{"key":"B135","article-title":"Sexually transmitted infections (STIs)","year":"2021"},{"key":"B136","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1146\/annurev-nutr-071816-064559","article-title":"Lipocalin 2: An emerging player in iron homeostasis and inflammation","volume":"37","author":"Xiao","year":"2017","journal-title":"Annu. Rev. Nutr."},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.71683.sa2","article-title":"Structural insight into the dual function of LbpB in mediating neisserial pathogenesis","volume":"10","author":"Yadav","year":"2021","journal-title":"Elife"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.02981","article-title":"Structural basis for evasion of nutritional immunity by the pathogenic Neisseriae","volume":"10","author":"Yadav","year":"2019","journal-title":"Front. Microbiol."},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087688","article-title":"Neisseria gonorrhoeae modulates iron-limiting innate immune defenses in macrophages","volume":"9","author":"Zughaier","year":"2014","journal-title":"PloS One"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.1017348\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T06:26:00Z","timestamp":1663223160000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.1017348\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,15]]},"references-count":139,"alternative-id":["10.3389\/fcimb.2022.1017348"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2022.1017348","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,15]]},"article-number":"1017348"}}