{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T08:30:39Z","timestamp":1783413039551,"version":"3.54.6"},"reference-count":83,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicines"],"abstract":"<jats:p>Background: Sexually transmitted gonorrhea, caused by the Gram-negative diplococcus Neisseria gonorrhoeae, continues to be a serious global health challenge despite efforts to eradicate it. Multidrug resistance among clinical N. gonorrhoeae isolates has limited treatment options, and attempts to develop vaccines have not been successful. Methods: A search of published literature was conducted, and information extracted to provide an update on the status of therapeutics and vaccine development for gonorrheal infection. Results: Recommended pharmacological treatment for gonorrhea has changed multiple times due to increasing acquisition of resistance to existing antibiotics by N. gonorrhoeae. Only broad-spectrum cephalosporin-based combination therapies are currently recommended for treatment of uncomplicated urogenital and anorectal gonococcal infections. With the reported emergence of ceftriaxone resistance, successful strategies addressing the global burden of gonorrhea must include vaccination. Century-old efforts at developing an effective vaccine against gonorrhea, leading to only four clinical trials, have not yielded any successful vaccine. Conclusions: While it is important to continue to explore new drugs for the treatment of gonorrhea, the historical trend of resistance acquisition suggests that any long-term strategy should include vaccine development. Advanced technologies in proteomics and in silico approaches to vaccine target identification may provide templates for future success.<\/jats:p>","DOI":"10.3390\/medicines8020011","type":"journal-article","created":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T08:33:48Z","timestamp":1612514028000},"page":"11","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Sexually Transmitted Neisseria gonorrhoeae Infections\u2014Update on Drug Treatment and Vaccine Development"],"prefix":"10.3390","volume":"8","author":[{"given":"Amber","family":"Jefferson","sequence":"first","affiliation":[{"name":"School of Pharmacy, College of Pharmacy &amp; Health Sciences, Campbell University, Buies Creek, NC 27506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Smith","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy &amp; Health Sciences, Campbell University, Buies Creek, NC 27506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3160-1824","authenticated-orcid":false,"given":"Pius S.","family":"Fasinu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy &amp; Health Sciences, Campbell University, Buies Creek, NC 27506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6017-8359","authenticated-orcid":false,"given":"Dorothea K.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy &amp; Health Sciences, Campbell University, Buies Creek, NC 27506, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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":"ref_2","unstructured":"WHO. World Health Organization (2016). WHO Guidelines for the Treatment of Neisseria Gonorrhoeae, WHO."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"548","DOI":"10.2471\/BLT.18.228486","article-title":"Chlamydia, gonorrhea, trichomoniasis and syphilis: Global prevalence and incidence estimates, 2016","volume":"97","author":"Rowley","year":"2019","journal-title":"Bull. World Health Organ."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"928","DOI":"10.3109\/1040841X.2015.1105782","article-title":"Is gonococcal disease preventable? The importance of understanding immunity and pathogenesis in vaccine development","volume":"42","author":"Edwards","year":"2016","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41572-019-0128-6","article-title":"Gonorrhoea","volume":"5","author":"Unemo","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_6","unstructured":"CDC. Center for Disease Control and Prevention (2019). Sexually Transmitted Disease Surveillance 2018."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.3389\/fimmu.2018.03187","article-title":"Human immune responses and the natural history of Neisseria gonorrhoeae infection","volume":"9","author":"Lovett","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1097\/MOH.0000000000000394","article-title":"Pathogenesis of Neisseria gonorrhoeae in the female reproductive tract: Neutrophilic host response, sustained infection, and clinical sequelae","volume":"25","author":"Stevens","year":"2018","journal-title":"Curr. Opin. Hematol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1053\/j.spid.2005.06.006","article-title":"Gonococcal infections in neonates and young children","volume":"16","author":"Woods","year":"2005","journal-title":"Semin. Ped. Infect. Dis."},{"key":"ref_10","unstructured":"Holmes, K.K. (2008). Gonococcal infection in the adult. Sexually Transmitted Diseases, McGraw-Hill."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1136\/sti.75.1.3","article-title":"From epidemiological synergy to public health policy and practice: The contribution of other sexually transmitted diseases to sexual transmission of HIV infection","volume":"75","author":"Fleming","year":"1999","journal-title":"Sex. Transm. Infect."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3937","DOI":"10.1128\/IAI.67.8.3937-3946.1999","article-title":"Limited local and systemic antibody responses to Neisseria gonorrhoeae during uncomplicated genital infections","volume":"67","author":"Hedges","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1093\/infdis\/153.3.520","article-title":"Bactericidal antibody response of normal human serum to the lipooligosaccharide of Neisseria gonorrhoeae","volume":"153","author":"Apicella","year":"1986","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1093\/jb\/mvi061","article-title":"Normal human sera contain bactericidal IgG that binds to the oligosaccharide epitope expressed within lipooligosaccharides of Neisseria gonorrhoeae","volume":"137","author":"Yamasaki","year":"2005","journal-title":"J. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2417","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":"ref_16","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/0882-4010(89)90112-5","article-title":"Sialylation of lipopolysaccharide and loss of absorption of bactericidal antibody during conversion of gonococci to serum resistance by CMP-N-acetylneuraminic acid","volume":"7","author":"Parsons","year":"1989","journal-title":"Microb. Pathog."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/S0171-2985(11)80352-9","article-title":"Lipo-oligosaccharides (LOS) of mucosal pathogens: Molecular mimicry and host-modification of LOS","volume":"187","author":"Mandrell","year":"1993","journal-title":"Immunobiology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1084\/jem.164.5.1735","article-title":"Immunoglobulin G antibodies directed against protein III block killing of serum-resistant Neisseria gonorrhoeae by immune serum","volume":"164","author":"Rice","year":"1986","journal-title":"J. Exp. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/mi.2012.12","article-title":"Neisseria gonorrhoeae selectively suppresses the development of Th1 and Th2 cells, and enhances Th17 cell responses, through TGF-beta-dependent mechanisms","volume":"5","author":"Liu","year":"2012","journal-title":"Mucosal Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/mi.2013.36","article-title":"Suppression of host adaptive immune responses by Neisseria gonorrhoeae: Role of interleukin 10 and type 1 regulatory T cells","volume":"7","author":"Liu","year":"2014","journal-title":"Mucosal Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e00095","DOI":"10.1128\/mBio.00095-11","article-title":"Diversion of the immune response to Neisseria gonorrhoeae from Th17 to Th1\/Th2 by treatment with anti-transforming growth factor beta antibody generates immunological memory and protective immunity","volume":"2","author":"Liu","year":"2011","journal-title":"mBio"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1517\/14656560902731993","article-title":"The use of cephalosporins for gonorrhea: The impending problem of resistance","volume":"10","author":"Barry","year":"2009","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Unemo, M. (2015). Current and future antimicrobial treatment of gonorrhoea \u2212 the rapidly evolving Neisseria gonorrhoeae continues to challenge. BMC Infect. Dis., 15.","DOI":"10.1186\/s12879-015-1029-2"},{"key":"ref_24","doi-asserted-by":"crossref","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":"ref_25","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1128\/CMR.00010-14","article-title":"Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: Past, evolution, and future","volume":"27","author":"Unemo","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2504","DOI":"10.1056\/NEJMc1512757","article-title":"Failure of dual antimicrobial therapy in treatment of gonorrhea","volume":"374","author":"Fifer","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S1473-3099(18)30340-2","article-title":"Genetic characterization of Neisseria gonorrhoeae resistant to both ceftriaxone and azithromycin","volume":"18","author":"Whiley","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/S0140-6736(01)32510-2","article-title":"The treatment of gonococcus infections by vaccines","volume":"174","author":"Eyre","year":"1909","journal-title":"Lancet"},{"key":"ref_29","first-page":"29","article-title":"Gonococcal vaccine studies in Inuvik","volume":"65","author":"Greenberg","year":"1974","journal-title":"Can. J. Public Health"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/0264-410X(91)90147-X","article-title":"Efficacy trial of a parenteral gonococcal pilus vaccine in men","volume":"9","author":"Boslego","year":"1991","journal-title":"Vaccine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S74","DOI":"10.1128\/CMR.2.Suppl.S74","article-title":"Gonococcal vaccines","volume":"2","author":"Tramont","year":"1989","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4532","DOI":"10.1016\/j.vaccine.2018.06.006","article-title":"Design and immune characterization of a novel Neisseria gonorrhoeae DNA vaccine using bacterial ghosts as vector and adjuvant","volume":"36","author":"Jiao","year":"2018","journal-title":"Vaccine"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Gala, R.P., Zaman, R.U., D\u2019Souza, M.J., and Zughaier, S.M. (2018). Novel whole-cell inactivated Neisseria gonorrhoeae microparticles as vaccine formulation in microneedle-based transdermal immunization. Vaccines, 6.","DOI":"10.20944\/preprints201807.0407.v1"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11109","DOI":"10.1073\/pnas.93.20.11109","article-title":"Analysis of the genetic differences between Neisseria meningitidis and Neisseria gonorrhoeae: Two closely related bacteria expressing two different pathogenicities","volume":"93","author":"Tinsley","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3389\/fimmu.2019.00137","article-title":"The Neisseria gonorrhoeae methionine sulfoxide reductase (MsrA\/B) is a surface exposed, immunogenic, vaccine candidate","volume":"10","author":"Jen","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/S0140-6736(17)31449-6","article-title":"Effectiveness of a group B outer membrane vesicle meningococcal vaccine against gonorrhoea in New Zealand: A retrospective case-control study","volume":"390","author":"Paynter","year":"2017","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"110","DOI":"10.7774\/cevr.2019.8.2.110","article-title":"A meningococcal B vaccine induces cross-protection against gonorrhea","volume":"8","author":"Azze","year":"2019","journal-title":"Clin. Exp. Vaccine Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1093\/cid\/ciy1061","article-title":"The serogroup B meningococcal vaccine Bexsero elicits antibodies to Neisseria gonorrhoeae","volume":"69","author":"Semchenko","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1074\/mcp.RA118.001125","article-title":"Quantitative proteomics of the 2016 WHO Neisseria gonorrhoeae reference strains surveys vaccine candidates and antimicrobial resistance determinants","volume":"18","author":"Zielke","year":"2019","journal-title":"Mol. Cell. Proteomics"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1073\/pnas.82.3.915","article-title":"Antibodies to peptides corresponding to a conserved sequence of gonococcal pilins block bacterial adhesion","volume":"82","author":"Rothbard","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1084\/jem.185.9.1557","article-title":"Several carcinoembryonic antigens (CD66) serve as receptors for gonococcal opacity proteins","volume":"185","author":"Chen","year":"1997","journal-title":"J. Exp. Med"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1084\/jem.193.3.281","article-title":"Binding of C4b-binding protein to porin: A molecular mechanism of serum resistance of Neisseria gonorrhoeae","volume":"193","author":"Ram","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4266","DOI":"10.1128\/IAI.00215-06","article-title":"Low-phosphate-dependent invasion resembles a general way for Neisseria gonorrhoeae to enter host cells","volume":"74","author":"Kuhlewein","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Cole, J.G., and Jerse, A.E. (2009). Functional characterization of antibodies against Neisseria gonorrhoeae opacity protein loops. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0008108"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1080\/21645515.2019.1609852","article-title":"Neisserial PorB immune enhancing activity and use as a vaccine adjuvant","volume":"15","author":"Yuen","year":"2019","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7247","DOI":"10.1016\/j.vaccine.2007.07.038","article-title":"Gonococcal transferrin binding protein chimeras induce bacteriocidal and growth inhibitory antibodies in mice","volume":"25","author":"Price","year":"2007","journal-title":"Vaccine"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1128\/CVI.05245-11","article-title":"Neisseria gonorrhoeae NspA induces specific bactericidal and opsonic antibodies in mice","volume":"18","author":"Li","year":"2011","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e00658","DOI":"10.1128\/IAI.00658-18","article-title":"Role of gonococcal neisserial surface protein A (NspA) in serum resistance and comparison of its factor H binding properties with those of its meningococcal counterpart","volume":"87","author":"Lewis","year":"2019","journal-title":"Infect. Immun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.3389\/fmicb.2018.02688","article-title":"2018. The MtrCDE efflux pump contributes to survival of Neisseria gonorrhoeae from human neutrophils and their antimicrobial components","volume":"9","author":"Handing","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jinf.2018.06.001","article-title":"Gonococcal MtrE and its surface-expressed loop 2 are immunogenic and elicit bactericidal antibodies","volume":"77","author":"Wang","year":"2018","journal-title":"J. Infect."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.bbrc.2012.12.132","article-title":"Recombinant truncated AniA of pathogenic Neisseria elicits a non-native immune response and functional blocking antibodies","volume":"431","author":"Shewell","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"K\u0142y\u017c, A., and Piekarowicz, A. (2018). Phage proteins are expressed on the surface of Neisseria gonorrhoeae and are potential vaccine candidates. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0202437"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/nrmicro.2017.169","article-title":"Neisseria gonorrhoeae host adaptation and pathogenesis","volume":"16","author":"Quillin","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1046\/j.1365-2958.1996.01551.x","article-title":"Carcinoembryonic antigens (CD66) on epithelial cells and neutrophils are receptors for Opa proteins of pathogenic Neisseriae","volume":"22","author":"Virji","year":"1996","journal-title":"Mol. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5576","DOI":"10.1128\/IAI.71.10.5576-5582.2003","article-title":"A gonococcal efflux pump system enhances bacterial survival in a female mouse model of genital tract infection","volume":"71","author":"Jerse","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1086\/522964","article-title":"Regulation of the MtrC-MtrD-MtrE efflux-pump system modulates the in vivo fitness of Neisseria gonorrhoeae","volume":"196","author":"Warner","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1111\/j.1365-2958.2008.06424.x","article-title":"Clinically relevant mutations that cause derepression of the Neisseria gonorrhoeae MtrC-MtrD-MtrE efflux pump system confer different levels of antimicrobial resistance and in vivo fitness","volume":"70","author":"Warner","year":"2008","journal-title":"Mol. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.3389\/fimmu.2018.02793","article-title":"Proteomics, bioinformatics and structure-function antigen mining for gonorrhea vaccines","volume":"9","author":"Baarda","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1074\/mcp.M116.058800","article-title":"Proteomics-driven antigen discovery for development of vaccines against gonorrhea","volume":"15","author":"Zielke","year":"2016","journal-title":"Mol. Cell. Proteomics"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e00898","DOI":"10.1128\/IAI.00898-16","article-title":"MetQ of Neisseria gonorrhoeae is a surface-expressed antigen that elicits bactericidal and functional blocking antibodies","volume":"85","author":"Semchenko","year":"2017","journal-title":"Infect. Immun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"8175","DOI":"10.1016\/j.vaccine.2020.10.077","article-title":"A novel gonorrhea vaccine composed of MetQ lipoprotein formulated with CpG shortens experimental murine infection","volume":"38","author":"Sikora","year":"2020","journal-title":"Vaccine"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e03046","DOI":"10.1128\/mBio.03046-19","article-title":"Repurposed drugs that block the gonococcus-complement receptor 3 interaction can prevent and cure gonococcal infection of primary human cervical epithelial cells","volume":"11","author":"Poole","year":"2020","journal-title":"mBio"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1093\/infdis\/174.6.1223","article-title":"Immunogenicity of Neisseria gonorrhoeae lipooligosaccharide epitope 2C7, widely expressed in vivo with no immunochemical similarity to human glycosphingolipids","volume":"174","author":"Gulati","year":"1996","journal-title":"J. Infect. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.vaccine.2005.07.065","article-title":"Characterization of a peptide vaccine candidate mimicking an oligosaccharide epitope of Neisseria gonorrhoeae and resultant immune responses and function","volume":"24","author":"Ngampasutadol","year":"2006","journal-title":"Vaccine"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Gulati, S., Zheng, B., Reed, G.W., Su, X., Cox, A.D., St. Michael, F., Stupak, J., Lewis, L.A., Ram, S., and Rice, P.A. (2013). Immunization against a saccharide epitope accelerates clearance of experimental gonococcal infection. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003559"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e02552","DOI":"10.1128\/mBio.02552-19","article-title":"Preclinical efficacy of a lipooligosaccharide peptide mimic candidate gonococcal vaccine","volume":"10","author":"Gulati","year":"2019","journal-title":"mBio"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"110172","DOI":"10.1016\/j.jtbi.2020.110172","article-title":"Identification of potential therapeutic targets in Neisseria gonorrhoeae by an in-silico approach","volume":"490","author":"Tanwer","year":"2020","journal-title":"J. Theor. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Zhu, T., McClure, R., Harrison, O.B., Genco, C., and Massari, P. (2019). Integrated bioinformatic analyses and immune characterization of new Neisseria gonorrhoeae vaccine antigens expressed during natural mucosal infection. Vaccines, 7.","DOI":"10.3390\/vaccines7040153"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1046\/j.1462-5822.2002.t01-1-00215.x","article-title":"A co-operative interaction between Neisseria gonorrhoeae and complement receptor 3 mediates infection of primary cervical epithelial cells","volume":"4","author":"Edwards","year":"2002","journal-title":"Cell Microbiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1111\/j.1462-5822.2011.01586.x","article-title":"Neisseria gonorrhoeae pilin glycan contributes to CR3 activation during challenge of primary cervical epithelial cells","volume":"13","author":"Jennings","year":"2011","journal-title":"Cell Microbiol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3233\/ISB-2009-0399","article-title":"In silico identification of candidate drug and vaccine targets from various pathways in Neisseria gonorrhoeae","volume":"9","author":"Barh","year":"2009","journal-title":"In Silico Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3389\/fchem.2014.00062","article-title":"Current challenges in peptide-based drug discovery","volume":"2","author":"Otvos","year":"2014","journal-title":"Front. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1096\/fj.201700613RR","article-title":"Self-derived structure-disrupting peptides targeting methionine aminopeptidase in pathogenic bacteria: A new strategy to generate antimicrobial peptides","volume":"33","author":"Zhan","year":"2019","journal-title":"FASEB J."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Li, L.H., Yen, M.Y., Ho, C.C., Wu, P., Wang, C.C., Maurya, P.K., Chen, P.S., Chen, W., Hsieh, W.Y., and Chen, H.W. (2013). Non-cytotoxic nanomaterials enhance antimicrobial activities of cefmetazole against multidrug-resistant Neisseria gonorrhoeae. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064794"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.ijantimicag.2015.05.016","article-title":"Alginate microbead-encapsulated silver complexes for selective delivery of broad-spectrum silver-based microbicides","volume":"46","author":"Damelin","year":"2015","journal-title":"Int. J. Antimicrob. Agents."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.3201\/eid2206.152091","article-title":"Neisseria gonorrhoeae resistant to ceftriaxone and cefixime, Argentina","volume":"22","author":"Gianecini","year":"2016","journal-title":"Emerg. Infect. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"381","DOI":"10.3201\/eid2402.171756","article-title":"Ceftriaxone-resistant Neisseria gonorrhoeae, Canada, 2017","volume":"24","author":"Lefebvre","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4520","DOI":"10.1016\/j.vaccine.2015.07.015","article-title":"The potential impact of vaccination on the prevalence of gonorrhea","volume":"33","author":"Craig","year":"2015","journal-title":"Vaccine"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/0882-4010(90)90071-W","article-title":"Neisseria gonorrhoeae colonises the genital tract of oestradiol-treated germ-free female mice","volume":"9","author":"Furr","year":"1990","journal-title":"Microb. Pathog."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5699","DOI":"10.1128\/IAI.67.11.5699-5708.1999","article-title":"Experimental gonococcal genital tract infection and opacity protein expression in estradiol-treated mice","volume":"67","author":"Jerse","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3389\/fmicb.2011.00124","article-title":"Vaccines for gonorrhea: Can we rise to the challenge?","volume":"2","author":"Zhu","year":"2011","journal-title":"Front. Microbiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1086\/315801","article-title":"Intranasal immunization with gonococcal outer membrane preparations reduces the duration of vaginal colonization of mice by Neisseria gonorrhoeae","volume":"182","author":"Plante","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4721","DOI":"10.1128\/AAC.49.11.4721-4732.2005","article-title":"Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity","volume":"49","author":"Dorr","year":"2005","journal-title":"Antimicrob. 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