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Emerging threat of antimicrobial resistance in Neisseria gonorrhoeae: pathogenesis, treatment challenges, and potential for vaccine development

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Abstract

The continuous rise of antimicrobial resistance (AMR) is a serious concern as it endangers the effectiveness of healthcare interventions that rely on antibiotics in the long run. The increasing resistance of Neisseria gonorrhoeae, the bacteria responsible for causing gonorrhea, to commonly used antimicrobial drugs, is a major concern. This has now become a critical global health crisis. In the coming years, there is a risk of a hidden epidemic caused by the emergence of gonococcal AMR. This will worsen the global situation. Infections caused by N. gonorrhoeae were once considered easily treatable. However, over time, they have become increasingly resistant to commonly used therapeutic medications, such as penicillin, ciprofloxacin, and azithromycin. As a result, this pathogen is developing into a true “superbug,” which means that ceftriaxone is now the only available option for initial empirical treatment. Effective management strategies are urgently needed to prevent severe consequences, such as infertility and pelvic inflammatory disease, which can result from delayed intervention. This review provides a thorough analysis of the escalating problem of N. gonorrhoeae, including its pathogenesis, current treatment options, the emergence of drug-resistant mechanisms, and the potential for vaccine development. We aim to provide valuable insights for healthcare practitioners, policymakers, and researchers in their efforts to combat N. gonorrhoeae antibiotic resistance by elucidating the multifaceted aspects of this global challenge.

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References

  • Ahrens K, Bradbury KJ, Bauer HM, Samuel MC, Gould G, Donatoni G, Higgins C, Kerndt P, Bolan G (2007) Trends in the use of sexually transmitted disease diagnostic technologies in California, 1996–2003. Sex Transm Dis 34:513–518

    Article  PubMed  Google Scholar 

  • Aitolo GL, Adeyemi OS, Afolabi BL, Owolabi AO (2021) Neisseria gonorrhoeae Antimicrobial Resistance: Past to Present to Future. Curr Microbiol 78:867–878

    Article  CAS  PubMed  Google Scholar 

  • Akasaka S, Muratani T, Yamada Y, Inatomi H, Takahashi K, Matsumoto T (2001) Emergence of cephem- and aztreonam-high-resistant Neisseria gonorrhoeae that does not produce beta-lactamase. J Infect Chemother off J Japan Soc Chemother 7:49–50

    Article  CAS  Google Scholar 

  • Almonacid-Mendoza HL, Humbert MV, Dijokaite A, Cleary DW, Soo Y, Hung M-C, Orr CM, Machelett MM, Tews I, Christodoulides M (2018) Structure of the Recombinant Neisseria gonorrhoeae Adhesin Complex Protein (rNg-ACP) and Generation of Murine Antibodies with Bactericidal Activity against Gonococci. mSphere. https://doi.org/10.1128/mSphere.00331-18

  • Anderson MT, Byerly L, Apicella MA, Steven Seifert H (2016) Seminal plasma promotes Neisseria gonorrhoeae aggregation and biofilm formation. J Bacteriol 198:2228–2235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anjum MF, Zankari E, Hasman H (2017) Molecular Methods for Detection of Antimicrobial Resistance. Microbiol Spectr. https://doi.org/10.1128/microbiolspec.ARBA-0011-2017

    Article  PubMed  Google Scholar 

  • Azze RFO (2019) A meningococcal B vaccine induces cross-protection against gonorrhea. Clin Exp Vaccine Res 8:110–115

    Article  PubMed  PubMed Central  Google Scholar 

  • Barbee LA, Golden MR (2020) Aztreonam for Neisseria gonorrhoeae: a systematic review and meta-analysis. J Antimicrob Chemother 75:1685–1688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barbee LA, St Cyr SB (2022) Management of Neisseria gonorrhoeae in the United States: Summary of Evidence From the Development of the 2020 Gonorrhea Treatment Recommendations and the 2021 Centers for Disease Control and Prevention Sexually Transmitted Infection Treatment Guidelines. Clin Infect Dis 74:S95–S111

    Article  CAS  PubMed  Google Scholar 

  • Barbee LA, Dombrowski JC, Kerani R, Golden MR (2014) Effect of nucleic acid amplification testing on detection of extragenital gonorrhea and chlamydial infections in men who have sex with men sexually transmitted disease clinic patients. Sex Transm Dis 41:168–172

    Article  PubMed  Google Scholar 

  • Bartlett JG, Gilbert DN, Spellberg B (2013) Seven ways to preserve the miracle of antibiotics. Clin Infect Dis an off Publ Infect Dis Soc Am 56:1445–1450

    Article  CAS  Google Scholar 

  • Basarab GS, Kern GH, McNulty J et al (2015) Responding to the challenge of untreatable gonorrhea: ETX0914, a first-in-class agent with a distinct mechanism-of-action against bacterial Type II topoisomerases. Sci Rep 5:11827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beggs GA, Zalucki YM, Brown NG, Rastegari S, Phillips RK, Palzkill T, Shafer WM, Kumaraswami M, Brennan RG (2019) Structural, Biochemical, and In Vivo Characterization of MtrR-Mediated Resistance to Innate Antimicrobials by the Human Pathogen Neisseria gonorrhoeae. J Bacteriol. https://doi.org/10.1128/JB.00401-19

    Article  PubMed  PubMed Central  Google Scholar 

  • Bester J, Pretorius E (2016) Effects of IL-1β, IL-6 and IL-8 on erythrocytes, platelets and clot viscoelasticity. Sci Rep 6:32188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Binnicker MJ, Jespersen DJ, Rollins LO (2011) Treponema-specific tests for serodiagnosis of syphilis: Comparative evaluation of seven assays. J Clin Microbiol 49:1313–1317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blair JMA, Richmond GE, Piddock LJV (2014) Multidrug efflux pumps in Gram-negative bacteria and their role in antibiotic resistance. Future Microbiol 9:1165–1177

    Article  CAS  PubMed  Google Scholar 

  • Bogdanić N, Močibob L, Vidović T, Soldo A, Begovać J (2022) Azithromycin consumption during the COVID-19 pandemic in Croatia, 2020. PLoS ONE 17:e0263437

    Article  PubMed  PubMed Central  Google Scholar 

  • Bradford PA, Miller AA, O’Donnell J, Mueller JP (2020) Zoliflodacin: An Oral Spiropyrimidinetrione Antibiotic for the Treatment of Neisseria gonorrheae, Including Multi-Drug-Resistant Isolates. ACS Infect Dis 6:1332–1345

    Article  CAS  PubMed  Google Scholar 

  • Bueno SA (2017) Improving the Detection and Surveillance of Sexually Transmitted Infections in Public Health Laboratories. 124

  • Burmeister AR (2015) Horizontal Gene Transfer. Evol Med Public Heal 2015:193–194

    Article  Google Scholar 

  • Cash DR, Noinaj N, Buchanan SK, Cornelissen CN (2015) Beyond the Crystal Structure: Insight into the Function and Vaccine Potential of TbpA Expressed by Neisseria gonorrhoeae. Infect Immun 83:4438–4449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Centers for Disease Control and Prevention (CDC) New data suggest STDs continued to increase during first year of the COVID-19 pandemic | CDC Online Newsroom | CDC. https://www.cdc.gov/media/releases/2022/p0412-STD-Increase.html. Accessed 15 May 2023

  • Chan PA, Robinette A, Montgomery M, Almonte A, Cu-Uvin S, Lonks JR, Chapin KC, Kojic EM, Hardy EJ (2016) Extragenital Infections Caused by Chlamydia trachomatis and Neisseria gonorrhoeae: A Review of the Literature. Infect Dis Obstet Gynecol 2016:5758387

    Article  PubMed  PubMed Central  Google Scholar 

  • Chateau A, Steven Seifert H (2016) Neisseria gonorrhoeae survives within and modulates apoptosis and inflammatory cytokine production of human macrophages. HHS Public Access 176:139–148

    Google Scholar 

  • Chaudhury A, Howe PH (2009) The tale of transforming growth factor-beta (TGFbeta) signaling: a soigné enigma. IUBMB Life 61:929–939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chbib C, Shah SM, Gala RP, Uddin MN (2021) Potential Applications of Microparticulate-Based Bacterial Outer Membrane Vesicles (OMVs) Vaccine Platform for Sexually Transmitted Diseases (STDs): Gonorrhea, Chlamydia, and Syphilis. Vaccines. https://doi.org/10.3390/vaccines9111245

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen Y, Gong Y, Yang T, Song X, Li J, Gan Y, Yin X, Lu Z (2016) Antimicrobial resistance in Neisseria gonorrhoeae in China: a meta-analysis. BMC Infect Dis 16:108

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen MY, McNulty A, Avery A et al (2019a) Solithromycin versus ceftriaxone plus azithromycin for the treatment of uncomplicated genital gonorrhoea (SOLITAIRE-U): a randomised phase 3 non-inferiority trial. Lancet Infect Dis 19:833–842

    Article  CAS  PubMed  Google Scholar 

  • Chen XS, Yin YP, Li XY (2019b) A ROADMAP plan to address research needs for gonococcal antimicrobial resistance in China. Clin Infect Dis 68:505–510

    Article  CAS  PubMed  Google Scholar 

  • Cho I, Yamanishi S, Cox L et al (2012) Antibiotics in early life alter the murine colonic microbiome and adiposity. Nature 488:621–626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Churchward CP, Alany RG, Kirk RS, Walker AJ, Snyder LAS (2017) Prevention of Ophthalmia Neonatorum Caused by Neisseria gonorrhoeae Using a Fatty Acid-Based Formulation. Mbio. https://doi.org/10.1128/mBio.00534-17

    Article  PubMed  PubMed Central  Google Scholar 

  • Ćmara J, Serra J, Ayats J, Bastida T, Carnicer-Pont D, Andreu A, Ardanuy C (2012) Molecular characterization of two high-level ceftriaxone-resistant Neisseria gonorrhoeae isolates detected in Catalonia, Spain. J Antimicrob Chemother 67:1858–1860

    Article  Google Scholar 

  • Cokkinis AJ, Mcelligott GLM (1938) SULPHANILAMIDE IN GONORRHŒA: AN ANALYSIS OF 633 CASES. Lancet 232:355–362

    Article  Google Scholar 

  • Connor DO, Zantow J, Hust M, Bier FF, von Nickisch-Rosenegk M (2016) Identification of Novel Immunogenic Proteins of Neisseria gonorrhoeae by Phage Display. PLoS ONE 11:e0148986

    Article  PubMed  PubMed Central  Google Scholar 

  • Cousin SJ, Whittington WLH, Roberts MC (2003) Acquired macrolide resistance genes in pathogenic Neisseria spp. isolated between 1940 and 1987. Antimicrob Agents Chemother 47:3877–3880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cox LM, Yamanishi S, Sohn J et al (2014) Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell 158:705–721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Craig AP, Gray RT, Edwards JL, Apicella MA, Jennings MP, Wilson DP, Seib KL (2015) The potential impact of vaccination on the prevalence of gonorrhea. Vaccine 33:4520–4525

    Article  PubMed  PubMed Central  Google Scholar 

  • Craiga AP, Graya RT, Edwardsb JL, Apicellac MA, Jenningsd MP, David P, Wilson a and KLS, (2015) The potential impact of vaccination on the prevalence of gonorrhea. HHS Public Access 176:139–148

    Google Scholar 

  • Cyr SS, Barbee L, Workowski KA, Bachmann LH, Pham C, Schlanger K (2020) Update to CDC’s Treatment Guidelines for Gonococcal Infection, 2020. Morb Mortal Wkly Rep Updat 69:1911–1916

    Article  Google Scholar 

  • Darling EK, McDonald H (2010) A meta-analysis of the efficacy of ocular prophylactic agents used for the prevention of gonococcal and chlamydial ophthalmia neonatorum. J Midwifery Womens Health 55:319–327

    Article  PubMed  Google Scholar 

  • Davies SC, Fowler T, Watson J, Livermore DM, Walker D (2013) Annual Report of the Chief Medical Officer: infection and the rise of antimicrobial resistance. Lancet 381:1606–1609

    Article  PubMed  Google Scholar 

  • de Vries HJC, Schim-van der Loeff MF (2019) Solithromycin for the treatment of drug-resistant gonorrhoea. Lancet Infect Dis 19:791–792

    Article  PubMed  Google Scholar 

  • Deguchi T, Yasuda M, Yokoi S et al (2003) Treatment of uncomplicated gonococcal urethritis by double-dosing of 200 mg cefixime at a 6-h interval. J Infect Chemother off J Japan Soc Chemother 9:35–39

    Article  CAS  Google Scholar 

  • Deng X, Klausner JD (2020) Six penA Codons Accurately and Reliably Predict Cefixime-Decreased Susceptibility in Neisseria gonorrhoeae. J Infect Dis 221:851–852

    Article  CAS  PubMed  Google Scholar 

  • Deng X, Allan-Blitz L-T, Klausner JD (2019) Using the genetic characteristics of Neisseria gonorrhoeae strains with decreased susceptibility to cefixime to develop a molecular assay to predict cefixime susceptibility. Sex Health 16:488–499

    Article  PubMed  PubMed Central  Google Scholar 

  • Derbie A, Mekonnen D, Woldeamanuel Y, Abebe T (2020) Azithromycin resistant gonococci: A literature review. Antimicrob Resist Infect Control 9:1–7

    Article  Google Scholar 

  • Dethlefsen L, Relman DA (2011) Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci U S A 108(Suppl):4554–4561

    Article  CAS  PubMed  Google Scholar 

  • Dethlefsen L, Huse S, Sogin ML, Relman DA (2008) The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol 6:e280

    Article  PubMed  PubMed Central  Google Scholar 

  • Dik J-WH, Hendrix R, Poelman R, Niesters HG, Postma MJ, Sinha B, Friedrich AW (2016) Measuring the impact of antimicrobial stewardship programs. Expert Rev Anti Infect Ther 14:569–575

    Article  CAS  PubMed  Google Scholar 

  • Dillon J, Parti R, Thakur S (2015) Antibiotic Resistance in Neisseria gonorrhoeae: Will Infections be Untreatable in the Future? Culture 35:1–8

    Google Scholar 

  • Donders GG, Desmyter J, De Wet DH, Van Assche FA (1993) The association of gonorrhoea and syphilis with premature birth and low birthweight. Genitourin Med 69:98–101

    CAS  PubMed  PubMed Central  Google Scholar 

  • Doron S, Davidson LE (2011) Antimicrobial stewardship. Mayo Clin Proc 86:1113–1123

    Article  PubMed  PubMed Central  Google Scholar 

  • Dougherty TJ (1986) Genetic analysis and penicillin-binding protein alterations in Neisseria gonorrhoeae with chromosomally mediated resistance. Antimicrob Agents Chemother 30:649–652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Douthwaite S, Champney WS (2001) Structures of ketolides and macrolides determine their mode of interaction with the ribosomal target site. J Antimicrob Chemother 48:1–8

    Article  CAS  PubMed  Google Scholar 

  • Du Y, Arvidson CG (2006) RpoH mediates the expression of some, but not all, genes induced in Neisseria gonorrhoeae adherent to epithelial cells. Infect Immun 74:2767–2776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duan H, Yu L, Tian F, Zhai Q, Fan L, Chen W (2022) Antibiotic-induced gut dysbiosis and barrier disruption and the potential protective strategies. Crit Rev Food Sci Nutr 62:1427–1452

    Article  CAS  PubMed  Google Scholar 

  • Edwards JL, Apicella MA (2004a) The Molecular Mechanisms Used by Neisseria gonorrhoeae To Initiate Infection Differ between Men and Women. Society 17:965–981

  • Edwards JL, Apicella MA (2004c) The molecular mechanisms used by Neisseria gonorrhoeae to initiate infection differ between men and women. Clin Microbiol Rev 17:965–81, table of contents

  • Edwards JL, Apicella MA (2004b) The molecular mechanisms used by Neisseria gonorrhoeae to initiate infection differ between men and women. Clin Microbiol Rev 17:965–981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elkashif A, Seleem MN (2020) Investigation of auranofin and gold-containing analogues antibacterial activity against multidrug-resistant Neisseria gonorrhoeae. Sci Rep 10:5602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • European Molecular Biology Laboratory (2021) Tackling the collateral damage from antibiotics: Scientists pave the way for reducing the harmful side effects antibiotics have on gut bacteria -- ScienceDaily. https://www.sciencedaily.com/releases/2021/10/211013114015.htm. Accessed 17 May 2023

  • Fairley CK, Hocking JS, Zhang L, Chow EPF (2017) Frequent transmission of gonorrhea in men who have sex with men. Emerg Infect Dis 23:102–104

    Article  PubMed  PubMed Central  Google Scholar 

  • Fang Y (2014) China should curb non-prescription use of antibiotics in the community. BMJ. https://doi.org/10.1136/bmj.g4233

    Article  PubMed  Google Scholar 

  • Farrell DJ, Sader HS, Rhomberg PR, Scangarella-Oman NE, Flamm RK (2017) In Vitro Activity of Gepotidacin (GSK2140944) against Neisseria gonorrhoeae. Antimicrob Agents Chemother. https://doi.org/10.1128/AAC.02047-16

    Article  PubMed  PubMed Central  Google Scholar 

  • Faruki H, Kohmescher RN, McKinney WP, Sparling PF (1985) A community-based outbreak of infection with penicillin-resistant Neisseria gonorrhoeae not producing penicillinase (chromosomally mediated resistance). N Engl J Med 313:607–611

    Article  CAS  PubMed  Google Scholar 

  • Fernandes P, Craft JC (2019) Phase 3 trial of treating gonorrhoea with solithromycin. Lancet Infect Dis 19:928

    Article  PubMed  Google Scholar 

  • Foerster S, Drusano G, Golparian D, Neely M, Piddock LJV, Alirol E, Unemo M (2019) In vitro antimicrobial combination testing of and evolution of resistance to the first-in-class spiropyrimidinetrione zoliflodacin combined with six therapeutically relevant antimicrobials for Neisseria gonorrhoeae. J Antimicrob Chemother 74:3521–3529

    Article  CAS  PubMed  Google Scholar 

  • Folster JP, Johnson PJT, Jackson L, Dhulipali V, Dyer DW, Shafer WM (2009) MtrR modulates rpoH expression and levels of antimicrobial resistance in Neisseria gonorrhoeae. J Bacteriol 191:287–297

    Article  CAS  PubMed  Google Scholar 

  • Forslund K, Sunagawa S, Kultima JR, Mende DR, Arumugam M, Typas A, Bork P (2013) Country-specific antibiotic use practices impact the human gut resistome. Genome Res 23:1163–1169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Foschi C, Salvo M, Cevenini R, Parolin C, Vitali B, Marangoni A (2017) Vaginal Lactobacilli Reduce Neisseria gonorrhoeae Viability through Multiple Strategies: An in Vitro Study. Front Cell Infect Microbiol 7:502

    Article  PubMed  PubMed Central  Google Scholar 

  • Gala RP, Zaman RU, D’Souza MJ, Zughaier SM (2018) Novel Whole-Cell Inactivated Neisseria gonorrhoeae Microparticles as Vaccine Formulation in Microneedle-Based Transdermal Immunization. Vaccines. https://doi.org/10.3390/vaccines6030060

    Article  PubMed  PubMed Central  Google Scholar 

  • Garrett NJ, McGrath N, Mindel A (2017) Advancing STI care in low/middle-income countries: has STI syndromic management reached its use-by date? Sex Transm Infect 93:4–5

    Article  PubMed  Google Scholar 

  • Golparian D, Fernandes P, Ohnishi M, Jensen JS, Unemo M (2012) In vitro activity of the new fluoroketolide solithromycin (CEM-101) against a large collection of clinical Neisseria gonorrhoeae isolates and international reference strains, including those with high-level antimicrobial resistance: potential treatment o. Antimicrob Agents Chemother 56:2739–2742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Golparian D, Shafer WM, Ohnishi M, Unemo M (2014) Importance of multidrug efflux pumps in the antimicrobial resistance property of clinical multidrug-resistant isolates of Neisseria gonorrhoeae. Antimicrob Agents Chemother 58:3556–3559

    Article  PubMed  PubMed Central  Google Scholar 

  • Gulati S, Shaughnessy J, Ram S, Rice PA (2019a) Targeting Lipooligosaccharide (LOS) for a Gonococcal Vaccine. Front Immunol 10:321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gulati S, Pennington MW, Czerwinski A et al (2019b) Preclinical Efficacy of a Lipooligosaccharide Peptide Mimic Candidate Gonococcal Vaccine. Mbio. https://doi.org/10.1128/mBio.02552-19

    Article  PubMed  PubMed Central  Google Scholar 

  • Han Y, Yin Y, Dai X et al (2020) Widespread Use of High-dose Ceftriaxone Therapy for Uncomplicated Gonorrhea Without Reported Ceftriaxone Treatment Failure: Results From 5 Years of Multicenter Surveillance Data in China. Clin Infect Dis an off Publ Infect Dis Soc Am 70:99–105

    Article  CAS  Google Scholar 

  • Health Department of Republic of South Africa (2015) Sexually Transmitted Infections Management Guidelines 2015.

  • Heel RNB and RC (1986) Aztreonam A Review of its Antibacterial Activity, Pharmacokinetic Properties and Therapeutic Use. ADIS Drug Inf. Serv. Auckl.

  • Hemarajata P, Yang S, Soge OO, Humphries RM, Klausner JD (2016) Performance and Verification of a Real-Time PCR Assay Targeting the gyrA Gene for Prediction of Ciprofloxacin Resistance in Neisseria gonorrhoeae. J Clin Microbiol 54:805–808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heumann CL, Quilter LAS, Eastment MC, Heffron R, Hawes SE (2017) Adverse Birth Outcomes and Maternal Neisseria gonorrhoeae Infection: A Population-Based Cohort Study in Washington State. Sex Transm Dis 44:266–271

    Article  PubMed  PubMed Central  Google Scholar 

  • Higashi DL, Lee SW, Snyder A, Weyand NJ, Bakke A, So M (2007) Dynamics of Neisseria gonorrhoeae attachment: microcolony development, cortical plaque formation, and cytoprotection. Infect Immun 75:4743–4753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Holmes KK, Johnson DW, Trostle HJ (1970) An estimate of the risk of men acquiring gonorrhea by sexual contact with infected females. Am J Epidemiol 91:170–174

    Article  CAS  PubMed  Google Scholar 

  • Hooper RR, Reynolds GH, Jones OG et al (1978) Cohort study of venereal disease. I: the risk of gonorrhea transmission from infected women to men. Am J Epidemiol 108:136–144

    Article  CAS  PubMed  Google Scholar 

  • Huband MD, Bradford PA, Otterson LG et al (2015) In vitro antibacterial activity of AZD0914, a new spiropyrimidinetrione DNA gyrase/topoisomerase inhibitor with potent activity against Gram-positive, fastidious Gram-Negative, and atypical bacteria. Antimicrob Agents Chemother 59:467–474

    Article  PubMed  Google Scholar 

  • Humbert MV, Christodoulides M (2018) Immunization with recombinant truncated Neisseria meningitidis-Macrophage Infectivity Potentiator (rT-Nm-MIP) protein induces murine antibodies that are cross-reactive and bactericidal for Neisseria gonorrhoeae. Vaccine 36:3926–3936

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ison CA, Hussey J, Sankar KN, Evans J, Alexander S (2011) Gonorrhoea treatment failures to cefixime and azithromycin in England, 2010. Euro Surveill. Bull. Eur. sur les Mal. Transm. = Eur. Commun. Dis. Bull. 16:

  • Iyer SS, Cheng G (2012) Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit Rev Immunol 32:23–63

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jacobsson S, Golparian D, Scangarella-Oman N, Unemo M (2018) In vitro activity of the novel triazaacenaphthylene gepotidacin (GSK2140944) against MDR Neisseria gonorrhoeae. J Antimicrob Chemother 73:2072–2077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jacobsson S, Kularatne R, Kittiyaowamarn R et al (2019) High in vitro susceptibility to the first-in-class spiropyrimidinetrione zoliflodacin among consecutive clinical Neisseria gonorrhoeae isolates from Thailand (2018) and South Africa (2015–2017). Antimicrob Agents Chemother. https://doi.org/10.1128/AAC.01479-19

    Article  PubMed  PubMed Central  Google Scholar 

  • Jacobsson S, Golparian D, Oxelbark J, Alirol E, Franceschi F, Gustafsson TN, Brown D, Louie A, Drusano G, Unemo M (2021) Pharmacodynamic Evaluation of Dosing, Bacterial Kill, and Resistance Suppression for Zoliflodacin Against Neisseria gonorrhoeae in a Dynamic Hollow Fiber Infection Model. Front Pharmacol 12:682135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jaffe HW, Biddle JW, Thornsberry C, Johnson RE, Kaufman RE, Reynolds GH, Wiesner PJ (1976) National gonorrhea therapy monitoring study: in vitro antibiotic susceptibility and its correlation with treatment results. N Engl J Med 294:5–9

    Article  CAS  PubMed  Google Scholar 

  • Jerse AE, Bash MC, Russell MW (2014) Vaccines against gonorrhea: current status and future challenges. Vaccine 32:1579–1587

    Article  CAS  PubMed  Google Scholar 

  • Jerse AE, Deal CD (2013) Vaccine research for gonococcal infections: where are we? Sex Transm Infect 89 Suppl 4:iv63–8

  • John CM, Li M, Feng D, Jarvis GA (2019) Cationic cell-penetrating peptide is bactericidal against Neisseria gonorrhoeae. J Antimicrob Chemother 74:3245–3251

    Article  CAS  PubMed  Google Scholar 

  • Jönsson A, Foerster S, Golparian D, Hamasuna R, Jacobsson S, Lindberg M, Jensen JS, Ohnishi M, Unemo M (2018) In vitro activity and time-kill curve analysis of sitafloxacin against a global panel of antimicrobial-resistant and multidrug-resistant Neisseria gonorrhoeae isolates. APMIS 126:29–37

    Article  PubMed  Google Scholar 

  • Kampmeier RH (1983) Introduction of sulfonamide therapy for gonorrhea. Sex Transm Dis 10:81–84

    Article  CAS  PubMed  Google Scholar 

  • Kenyon C (2019) Comment on “Effectiveness of a Group B outer membrane vesicle meningococcal vaccine in preventing hospitalization from gonorrhea in New Zealand: a retrospective cohort study, Vaccines, 2019, 1, 5; doi:https://doi.org/10.3390/vaccines7010005”. Vaccines. https://doi.org/10.3390/vaccines7010031

  • Kolář M, Urbánek K, Látal T (2001) Antibiotic selective pressure and development of bacterial resistance. Int J Antimicrob Agents 17:357–363

    Article  PubMed  Google Scholar 

  • Kularatne R, Maseko V, Gumede L, Kufa T (2018) Trends in Neisseria gonorrhoeae Antimicrobial Resistance over a Ten-Year Surveillance Period, Johannesburg, South Africa, 2008−2017. Antibiot (Basel, Switzerland). https://doi.org/10.3390/antibiotics7030058

  • Kulp A, Kuehn MJ (2010) Biological functions and biogenesis of secreted bacterial outer membrane vesicles. Annu Rev Microbiol 64:163–184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar S (2020) In silico identification of novel tuberculosis drug targets in mycobacterium tuberculosis P450 enzymes by interaction study with Azole drugs. Malaysian J Med Heal Sci 16:24–30

    Google Scholar 

  • Lau A, Kong FYS, Huston W, Chow EPF, Fairley CK, Hocking JS (2019) Factors associated with anorectal Chlamydia trachomatis or Neisseria gonorrhoeae test positivity in women: a systematic review and meta-analysis. Sex Transm Infect 95:361–367

    Article  PubMed  Google Scholar 

  • Lewis DA (2014) Global resistance of Neisseria gonorrhoeae: when theory becomes reality. Curr Opin Infect Dis 27:62–67

    Article  CAS  PubMed  Google Scholar 

  • Lin H, Dyar OJ, Rosales-Klintz S, Zhang J, Tomson G, Hao M, Stålsby Lundborg C (2016) Trends and patterns of antibiotic consumption in Shanghai municipality, China: a 6 year surveillance with sales records, 2009–14. J Antimicrob Chemother 71:1723–1729

    Article  CAS  PubMed  Google Scholar 

  • Lin EY, Adamson PC, Deng X, Klausner JD (2021) Establishing Novel Molecular Algorithms to Predict Decreased Susceptibility to Ceftriaxone in Neisseria gonorrhoeae Strains. J Infect Dis 223:1232–1240

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Islam EA, Jarvis GA, Gray-Owen SD, Russell MW (2012) Neisseria gonorrhoeae selectively suppresses the development of Th1 and Th2 cells, and enhances Th17 cell responses, through TGF-β-dependent mechanisms. Mucosal Immunol 5:320–331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu B, Roberts CL, Clarke M, Jorm L, Hunt J, Ward J (2013) Chlamydia and gonorrhoea infections and the risk of adverse obstetric outcomes: a retrospective cohort study. Sex Transm Infect 89:672–678

    Article  PubMed  Google Scholar 

  • Liu Y, Liu W, Russell MW (2014) Suppression of host adaptive immune responses by Neisseria gonorrhoeae: role of interleukin 10 and type 1 regulatory T cells. Mucosal Immunol 7:165–176

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Perez J, Hammer LA, Gallagher HC, De Jesus M, Egilmez NK, Russell MW (2018) Intravaginal Administration of Interleukin 12 during Genital Gonococcal Infection in Mice Induces Immunity to Heterologous Strains of Neisseria gonorrhoeae. mSphere. https://doi.org/10.1128/mSphere.00421-17

  • Llata E, Braxton J, Asbel L, Chow J, Jenkins L, Murphy R, Pathela P, Schumacher C, Torrone E (2018) Rectal Chlamydia trachomatis and Neisseria gonorrhoeae Infections Among Women Reporting Anal Intercourse. Obstet Gynecol 132:692–697

    Article  PubMed  PubMed Central  Google Scholar 

  • Lu S, Grimes-Serrano JM, Wang S (2009) DNA Vaccines for Biodefense and Emerging and Neglected Infectious Diseases. Vaccines Biodefense Emerg Neglected Dis 93–114

  • Lucío MI, Kyriazi M-E, Hamilton J, Batista D, Sheppard A, Sams-Dodd E, Humbert MV, Hussain I, Christodoulides M, Kanaras AG (2020) Bactericidal Effect of 5-Mercapto-2-nitrobenzoic Acid-Coated Silver Nanoclusters against Multidrug-Resistant Neisseria gonorrhoeae. ACS Appl Mater Interfaces 12:27994–28003

    Article  PubMed  Google Scholar 

  • Mahoney JF, Ferguson C, Buchholtz M, Van Slyke CJ et al (1943) The Use of Penicillin Sodium in the Treatment of Sulfonamide. Resistant Gonorrhoea in Men. A Preliminary Report Am J Syph 27:525–528

    Google Scholar 

  • Maurakis SA, Cornelissen CN (2022) Recent Progress Towards a Gonococcal Vaccine. Front Cell Infect Microbiol 12:881392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maxwell GL, Watson WJ (1992) Preterm premature rupture of membranes: results of expectant management in patients with cervical cultures positive for group B streptococcus or Neisseria gonorrhoeae. Am J Obstet Gynecol 166:945–949

    Article  CAS  PubMed  Google Scholar 

  • Morse SA, Johnson SR, Biddle JW, Roberts MC (1986) High-level tetracycline resistance in Neisseria gonorrhoeae is result of acquisition of streptococcal tetM determinant. Antimicrob Agents Chemother 30:664–670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Munson E, Firmani MA (2009) Molecular diagnosis of Neisseria gonorrhoeae infection in the United States. Expert Opin Med Diagn 3:327–343

    Article  CAS  PubMed  Google Scholar 

  • Murray CJL, Ikuta KS, Sharara F et al (2022) Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet 399:629–655

    Article  CAS  Google Scholar 

  • O’Donnell J, Lawrence K, Vishwanathan K, Hosagrahara V, Mueller JP (2019) Single-Dose Pharmacokinetics, Excretion, and Metabolism of Zoliflodacin, a Novel Spiropyrimidinetrione Antibiotic, in Healthy Volunteers. Antimicrob Agents Chemother. https://doi.org/10.1128/AAC.01808-18

    Article  PubMed  PubMed Central  Google Scholar 

  • of Sexually Transmitted Infection JS (2011) Gonococcal infection. Sexually transmitted infections, diagnosis and treatment guidelines 2011. Jpn J Sex Transm Dis 22:529

  • Ohnishi M, Watanabe Y, Ono E, Takahashi C, Oya H, Kuroki T, Shimuta K, Okazaki N, Nakayama S, Watanabe H (2010) Spread of a chromosomal cefixime-resistant penA gene among different Neisseria gonorrhoeae lineages. Antimicrob Agents Chemother 54:1060–1067

    Article  CAS  PubMed  Google Scholar 

  • Ohnishi M, Golparian D, Shimuta K, Saika T, Hoshina S, Iwasaku K, Nakayama S, Kitawaki J, Unemo M (2011) Is Neisseria gonorrhoeae initiating a future era of untreatable gonorrhea?: detailed characterization of the first strain with high-level resistance to ceftriaxone. Antimicrob Agents Chemother 55:3538–3545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Omeershffudin Umairah Natasya Mohd Kumar Suresh (2022) Antimicrobial resistance in Klebsiella pneumoniae: identification of bacterial DNA adenine methyltransferase as a novel drug target from hypothetical proteins using subtractive genomics. Genomics Inf 20:e47-

  • Omeershffudin Umairah Natasya Mohd Kumar Suresh (2023) Antibiotic Resistance in Neisseria Gonnorhoeae:A Broad-spectrum Drug Target Identification by Using Subtractive Genomics. Genomics Inform.

  • Ortiz M, Edgardo Santander P, Judith Lugo P (2021) Neisseria gonorrhoeae: a wayward pathogen. Microbiological concepts, antimicrobial resistance and its epidemiological surveillance in Chile. Rev Chilena Infectol 38:512–522

    Article  Google Scholar 

  • Palleja A, Mikkelsen KH, Forslund SK et al (2018) Recovery of gut microbiota of healthy adults following antibiotic exposure. Nat Microbiol 3:1255–1265

    Article  CAS  PubMed  Google Scholar 

  • Paterson DL (2004) “Collateral Damage” from Cephalosporin or Quinolone Antibiotic Therapy. Clin Infect Dis 38:S341–S345

    Article  CAS  PubMed  Google Scholar 

  • Petousis-Harris H, Paynter J, Morgan J, Saxton P, McArdle B, Goodyear-Smith F, Black S (2017) Effectiveness of a group B outer membrane vesicle meningococcal vaccine against gonorrhoea in New Zealand: a retrospective case-control study. Lancet 390:1603–1610

    Article  CAS  PubMed  Google Scholar 

  • Poole J, Day CJ, Haselhorst T, Jen FE-C, Torres VJ, Edwards JL, Jennings MP (2020) Repurposed Drugs That Block the Gonococcus-Complement Receptor 3 Interaction Can Prevent and Cure Gonococcal Infection of Primary Human Cervical Epithelial Cells. Mbio. https://doi.org/10.1128/mBio.03046-19

    Article  PubMed  PubMed Central  Google Scholar 

  • Prestinaci F, Pezzotti P, Pantosti A (2015) Antimicrobial resistance: a global multifaceted phenomenon. Pathog Glob Health 109:309–318

    Article  PubMed  PubMed Central  Google Scholar 

  • Price GA, Russell MW, Cornelissen CN (2005) Intranasal administration of recombinant Neisseria gonorrhoeae transferrin binding proteins A and B conjugated to the cholera toxin B subunit induces systemic and vaginal antibodies in mice. Infect Immun 73:3945–3953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ram S, Cullinane M, Blom AM et al (2001) Binding of C4b-binding protein to porin: A molecular mechanism of serum resistance of Neisseria gonorrhoeae. J Exp Med 193:281–295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Read AF, Woods RJ (2014) Antibiotic resistance management. Evol Med Public Heal 2014:147

    Article  Google Scholar 

  • Rice PA, Shafer WM, Ram S, Jerse AE (2017a) Neisseria gonorrhoeae: Drug Resistance, Mouse Models, and Vaccine Development. Annu Rev Microbiol 71:665–686

    Article  CAS  PubMed  Google Scholar 

  • Rice PA, Shafer WM, Ram S, Jerse AE (2017b) Neisseria gonorrhoeae : Drug Resistance, Mouse Models, and Vaccine Development. Annu Rev Microbiol 71:665–686

    Article  CAS  PubMed  Google Scholar 

  • Rimington C (1960) Spectral-absorption coefficients of some porphyrins in the Soret-band region. Biochem J 75:620–623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roodgar M, Good BH, Garud NR et al (2021) Longitudinal linked-read sequencing reveals ecological and evolutionary responses of a human gut microbiome during antibiotic treatment. Genome Res 31:1433–1446

    Article  PubMed  PubMed Central  Google Scholar 

  • Rotman E, Seifert HS (2014) The genetics of Neisseria species. Annu Rev Genet 48:405–431

    Article  CAS  PubMed  Google Scholar 

  • Ruiz VE, Battaglia T, Kurtz ZD et al (2017) A single early-in-life macrolide course has lasting effects on murine microbial network topology and immunity. Nat Commun 8:518

    Article  PubMed  PubMed Central  Google Scholar 

  • Russell MW (2021) Immune Responses to Neisseria gonorrhoeae: Challenges and Opportunities With Respect to Pelvic Inflammatory Disease. J Infect Dis 224:S96–S102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Russell C, Rahman A, Mohammed AR (2013) Application of genomics, proteomics and metabolomics in drug discovery, development and clinic. Ther Deliv 4:395–413

    Article  CAS  PubMed  Google Scholar 

  • Sabat R, Grütz G, Warszawska K, Kirsch S, Witte E, Wolk K, Geginat J (2010) Biology of interleukin-10. Cytokine Growth Factor Rev 21:331–344

    Article  CAS  PubMed  Google Scholar 

  • Scangarella-Oman NE, Hossain M, Perry CR, Tiffany C, Powell M, Swift B, Dumont EF (2023) Dose selection for a phase III study evaluating gepotidacin (GSK2140944) in the treatment of uncomplicated urogenital gonorrhoea. Sex Transm Infect 99:64–69

    Article  PubMed  Google Scholar 

  • Seifert QSJ, HS, (2017) Neisseria gonoorrhoeae host-adaptation and pathogenesis. Physiol Behav 176:139–148

    Google Scholar 

  • Semchenko EA, Mubaiwa TD, Day CJ, Seib KL (2020) Role of the Gonococcal Neisserial Heparin Binding Antigen in Microcolony Formation, and Serum Resistance and Adherence to Epithelial Cells. J Infect Dis 221:1612–1622

    Article  CAS  PubMed  Google Scholar 

  • Serra-Pladevall J, Barberá MJ, Callarisa AE, Bartolomé-Comas R, Andreu A (2017) Differences in Neisseria gonorrhoeae population structure and antimicrobial resistance pattern between men who have sex with men and heterosexuals. Epidemiol Infect 145:379–385

    Article  CAS  PubMed  Google Scholar 

  • Shafer WM, Yu EW, Rouquette-loughlin C, Golparian D, Jerse AE, Unemo M (2016) Efflux Pumps in Neisseria gonorrhoeae : Contributions to Antimicrobial Resistance and Virulence. Efflux-Mediated Antimicrob Resist Bact. https://doi.org/10.1007/978-3-319-39658-3

    Article  Google Scholar 

  • Shaskolskiy B, Kandinov I, Dementieva E, Gryadunov D (2022) Antibiotic Resistance in Neisseria gonorrhoeae: Challenges in Research and Treatment. Microorganisms. https://doi.org/10.3390/microorganisms10091699

    Article  PubMed  PubMed Central  Google Scholar 

  • Shewell LK, Ku SC, Schulz BL, Jen FE-C, Mubaiwa TD, Ketterer MR, Apicella MA, Jennings MP (2013) Recombinant truncated AniA of pathogenic Neisseria elicits a non-native immune response and functional blocking antibodies. Biochem Biophys Res Commun 431:215–220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shortridge VD, Flamm RK, Ramer N, Beyer J, Tanaka SK (1996) Novel mechanism of macrolide resistance in Streptococcus pneumoniae. Diagn Microbiol Infect Dis 26:73–78

    Article  CAS  PubMed  Google Scholar 

  • Siedner MJ, Pandori M, Castro L, Barry P, Whittington WLH, Liska S, Klausner JD (2007) Real-time PCR assay for detection of quinolone-resistant Neisseria gonorrhoeae in urine samples. J Clin Microbiol 45:1250–1254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sikora AE, Mills RH, Weber JV, Hamza A, Passow BW, Romaine A, Williamson ZA, Reed RW, Zielke RA, Korotkov KV (2017) Peptide Inhibitors Targeting the Neisseria gonorrhoeae Pivotal Anaerobic Respiration Factor AniA. Antimicrob Agents Chemother. https://doi.org/10.1128/AAC.00186-17

    Article  PubMed  PubMed Central  Google Scholar 

  • Sikora AE, Gomez C, Le Van A, Baarda BI, Darnell S, Martinez FG, Zielke RA, Bonventre JA, Jerse AE (2020) A novel gonorrhea vaccine composed of MetQ lipoprotein formulated with CpG shortens experimental murine infection. Vaccine 38:8175–8184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh V, Bala M, Bhargava A, Kakran M, Bhatnagar R (2018a) In vitro efficacy of 21 dual antimicrobial combinations comprising novel and currently recommended combinations for treatment of drug resistant gonorrhoea in future era. PLoS ONE 13:e0193678

    Article  PubMed  PubMed Central  Google Scholar 

  • Singh V, Bala M, Bhargava A, Kakran M, Bhatnagar R (2018b) In Vitro Synergy Testing of Gentamicin, an Old Drug Suggested as Future Treatment Option for Gonorrhoea, in Combination With Six Other Antimicrobials Against Multidrug-Resistant Neisseria gonorrhoeae Strains. Sex Transm Dis 45:127–131

    Article  CAS  PubMed  Google Scholar 

  • Singh S, Verma N, Taneja N (2019) The human gut resistome: Current concepts & future prospects. Indian J Med Res 150:345–358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Soge OO, Salipante SJ, No D, Duffy E, Roberts MC (2016) In Vitro Activity of Delafloxacin against Clinical Neisseria gonorrhoeae Isolates and Selection of Gonococcal Delafloxacin Resistance. Antimicrob Agents Chemother 60:3106–3111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sóki J, Wybo I, Hajdú E et al (2020) A Europe-wide assessment of antibiotic resistance rates in Bacteroides and Parabacteroides isolates from intestinal microbiota of healthy subjects. Anaerobe 62:102182

    Article  PubMed  Google Scholar 

  • Spellberg B, Gilbert DN (2014) The future of antibiotics and resistance: a tribute to a career of leadership by John Bartlett. Clin Infect Dis an off Publ Infect Dis Soc Am 59(Suppl 2):S71–S75

    Article  CAS  Google Scholar 

  • Spurbeck RR, Arvidson CG (2010) Lactobacillus jensenii surface-associated proteins inhibit Neisseria gonorrhoeae adherence to epithelial cells. Infect Immun 78:3103–3111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suay-García B, Pérez-Gracia MT (2018) Future Prospects for Neisseria gonorrhoeae Treatment. Antibiot (Basel, Switzerland). https://doi.org/10.3390/antibiotics7020049

  • Suay-García B, Pérez-Gracia MT (2017) Drug-resistant Neisseria gonorrhoeae: latest developments. Eur J Clin Microbiol Infect Dis 36:1065–1071

    Article  PubMed  Google Scholar 

  • Sun Y, Zhang J, Zhang Y, Liu J, van der Veen S, Duttwyler S (2018) The closo-Dodecaborate Dianion Fused with Oxazoles Provides 3D Diboraheterocycles with Selective Antimicrobial Activity. Chemistry 24:10364–10371

    Article  CAS  PubMed  Google Scholar 

  • Sutcliffe J, Tait-Kamradt A, Wondrack L (1996) Streptococcus pneumoniae and Streptococcus pyogenes resistant to macrolides but sensitive to clindamycin: a common resistance pattern mediated by an efflux system. Antimicrob Agents Chemother 40:1817–1824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanaka M, Nakayama H, Tunoe H, Egashira T, Kanayama A, Saika T, Kobayashi I, Naito S (2002) A remarkable reduction in the susceptibility of Neisseria gonorrhoeae isolates to cephems and the selection of antibiotic regimens for the single-dose treatment of gonococcal infection in Japan. J Infect Chemother off J Japan Soc Chemother 8:81–86

    Article  CAS  Google Scholar 

  • Tanielian C, Schweitzer C, Mechin R, Wolff C (2001) Quantum yield of singlet oxygen production by monomeric and aggregated forms of hematoporphyrin derivative. Free Radic Biol Med 30:208–212

    Article  CAS  PubMed  Google Scholar 

  • Taylor SN, Morris DH, Avery AK et al (2018) Gepotidacin for the Treatment of Uncomplicated Urogenital Gonorrhea: A Phase 2, Randomized, Dose-Ranging, Single-Oral Dose Evaluation. Clin Infect Dis an off Publ Infect Dis Soc Am 67:504–512

    Article  CAS  Google Scholar 

  • Terreni M, Taccani M, Pregnolato M (2021) New Antibiotics for Multidrug-Resistant Bacterial Strains: Latest Research Developments and Future Perspectives. Molecules. https://doi.org/10.3390/MOLECULES26092671

    Article  PubMed  PubMed Central  Google Scholar 

  • Tobiason DM, Seifert HS (2006) The obligate human pathogen, Neisseria gonorrhoeae, is polyploid. PLoS Biol 4:1069–1078

    Article  CAS  Google Scholar 

  • Townsend L, Hughes G, Kerr C, Kelly M, O’Connor R, Sweeney E, Doyle C, O’Riordan R, Bergin C, Bannan C (2020) Bacterial pneumonia coinfection and antimicrobial therapy duration in SARS-CoV-2 (COVID-19) infection. JAC-antimicrobial Resist 2:dlaa071

  • Umairah O, Suresh K (2019) In silico approach for mining of potential drug targets from hypothetical proteins of bacterial proteome. Int J Mol Biol 4:145–152

    Google Scholar 

  • Unemo M, Shafer WM (2014) Antimicrobial resistance in Neisseria gonorrhoeae in the 21st Century: Past, evolution, and future. Clin Microbiol Rev 27:587–613

    Article  PubMed  PubMed Central  Google Scholar 

  • Unemo M, Workowski K (2018) Dual antimicrobial therapy for gonorrhoea: what is the role of azithromycin? Lancet Infect Dis 18:486–488

    Article  PubMed  PubMed Central  Google Scholar 

  • Unemo M, Golparian D, Nicholas R, Ohnishi M, Gallay A, Sednaouie P (2012) High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: Novel penA mosaic allele in a successful international clone causes treatment failure. Antimicrob Agents Chemother 56:1273–1280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Unemo M, Golparian D, Shafer WM (2014) Challenges with gonorrhea in the era of multi-drug and extensively drug resistance - are we on the right track? Expert Rev Anti Infect Ther 12:653–656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Unemo M, Ringlander J, Wiggins C, Fredlund H, Jacobsson S, Cole M (2015) High in vitro susceptibility to the novel spiropyrimidinetrione ETX0914 (AZD0914) among 873 contemporary clinical Neisseria gonorrhoeae isolates from 21 European countries from 2012 to 2014. Antimicrob Agents Chemother 59:5220–5225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Unemo M, del Rio C, Shafer WM (2016) Antimicrobial Resistance Expressed by Neisseria gonorrhoeae: A Major Global Public Health Problem in the 21st Century. Emerg Infect 10:213–237

    Article  CAS  Google Scholar 

  • Unemo M, Golparian D, Eyre DW (2019a) Antimicrobial Resistance in Neisseria gonorrhoeae and Treatment of Gonorrhea. Methods Mol Biol 1997:37–58

    Article  CAS  PubMed  Google Scholar 

  • Unemo M, Lahra MM, Cole M, Galarza P, Ndowa F, Martin I, Dillon J-AR, Ramon-Pardo P, Bolan G, Wi T (2019b) World Health Organization Global Gonococcal Antimicrobial Surveillance Program (WHO GASP): review of new data and evidence to inform international collaborative actions and research efforts. Sex Health 16:412–425

    Article  PubMed  PubMed Central  Google Scholar 

  • Unemo M, Lahra MM, Escher M et al (2021) WHO global antimicrobial resistance surveillance for Neisseria gonorrhoeae 2017–18: a retrospective observational study. The Lancet Microbe 2:e627–e636

    Article  CAS  PubMed  Google Scholar 

  • Van Boeckel TP, Gandra S, Ashok A, Caudron Q, Grenfell BT, Levin SA, Laxminarayan R (2014) Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect Dis 14:742–750

    Article  PubMed  Google Scholar 

  • van Slyke CJ, Wolcott RR, Mahoney JF (1941) THE CHEMOTHERAPY OF GONOCOCCIC INFECTIONS: I. SUMMARY OF EXPERIENCE WITH SULFANILAMIDE II. INVESTIGATION OF CHEMOTHERAPEUTIC EFFECT OF SULFAPYRIDINE. J Am Med Assoc 116:276–280

    Article  Google Scholar 

  • Ventola CL (2015) The antibiotic resistance crisis: part 1: causes and threats. P T 40:277–283

    PubMed  PubMed Central  Google Scholar 

  • Walker CK, Sweet RL (2011) Gonorrhea infection in women: prevalence, effects, screening, and management. Int J Womens Health 3:197–206

    PubMed  PubMed Central  Google Scholar 

  • Wang S, Xue J, Lu P, Ni C, Cheng H, Han R, van der Veen S (2018) Gonococcal MtrE and its surface-expressed Loop 2 are immunogenic and elicit bactericidal antibodies. J Infect 77:191–204

    Article  PubMed  Google Scholar 

  • Wang Y, Ferrer-Espada R, Baglo Y, Goh XS, Held KD, Grad YH, Gu Y, Gelfand JA, Dai T (2019) Photoinactivation of Neisseria gonorrhoeae: A Paradigm-Changing Approach for Combating Antibiotic-Resistant Gonococcal Infection. J Infect Dis 220:873–881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whelan J, Kløvstad H, Haugen IL, van Holle MR-DR, B, Storsaeter J, (2016) Ecologic Study of Meningococcal B Vaccine and Neisseria gonorrhoeae Infection, Norway. Emerg Infect Dis 22:1137–1139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • White RG, Moodley P, McGrath N, Hosegood V, Zaba B, Herbst K, Newell M, Sturm WA, Hayes RJ (2008) Low effectiveness of syndromic treatment services for curable sexually transmitted infections in rural South Africa. Sex Transm Infect 84:528–534

    Article  CAS  PubMed  Google Scholar 

  • WHO (World Health Organization) (2012) Global action plan to control the spread and impact of antimicrobial resistance in Neisseria gonorrhoeae.

  • WHO (World Health Organization) (2016) Global health sector strategy on Sexually Transmitted Infections, 2016–2021 ; Towards Ending STI. World Heal Organ. https://doi.org/10.1055/s-2007-970201

  • WHO (2021) Enhanced gonococcal antimicrobial surveillance programme (EGASP): general protocol.

  • Willcox RR (1970) A survey of problems in the antibiotic treatment of gonorrhoea. With special reference to South-East Asia. Br J Vener Dis 46:217–242

    CAS  PubMed  PubMed Central  Google Scholar 

  • World Health Organization (WHO) (2016) WHO GUIDELINES FOR THE Treatment of Neisseria gonorrhoeae.

  • World Health Organization (WHO) (2019) Global Antimicrobial Resistance Surveillance System (GLASS): molecular methods for antimicrobial resistance (AMR) diagnostics to enhance the Global Antimicrobial Resistance Surveillance System. World Health Organization

  • World Health Organization (WHO) (2022a) Multi-drug resistant gonorrhoea. https://www.who.int/news-room/fact-sheets/detail/multi-drug-resistant-gonorrhoea. Accessed 14 May 2023

  • World Health Organization (WHO) (2022b) Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report 2022b.

  • World Health Organization (WHO) (2022c) Multi-drug resistant gonorrhoea. https://www.who.int/news-room/fact-sheets/detail/multi-drug-resistant-gonorrhoea. Accessed 3 Feb 2022c

  • World Health Organization (WHO) (2022d) Global Health Sector Strategies on, respectively, HIV, viral hepatitis and sexually transmitted infections for the period 2022d–2030 (GHSS).

  • World Health Organization (WHO) (2023a) GASP Network. https://www.who.int/initiatives/gonococcal-antimicrobial-surveillance-programme/gasp-network. Accessed 18 May 2023a

  • World Health Organization (WHO) (2023) WHO Gonococcal AMR Surveillance Programme (WHO-GASP). https://www.who.int/data/gho/data/themes/topics/who-gonococcal-amr-surveillance-programme-who-gasp. Accessed 18 May 2023

  • Yokoi S, Deguchi T, Ozawa T, Yasuda M, Ito S, Kubota Y, Tamaki M, Maeda S (2007) Threat to cefixime treatment for gonorrhea. Emerg Infect Dis 13:1275–1277

    PubMed  PubMed Central  Google Scholar 

  • Yosef I, Manor M, Qimron U (2016) Counteracting Selection for Antibiotic-Resistant Bacteria Bacteriophage 6:e1096996

    CAS  PubMed  Google Scholar 

  • Zeshan B, Karobari MI, Afzal N, et al (2021) The Usage of Antibiotics by COVID-19 Patients with Comorbidities: The Risk of Increased Antimicrobial Resistance. Antibiot (Basel, Switzerland). https://doi.org/10.3390/antibiotics11010035

  • Zhang J-M, An J (2007) Cytokines, inflammation, and pain. Int Anesthesiol Clin 45:27–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu W, Chen C-J, Thomas CE, Anderson JE, Jerse AE, Sparling PF (2011) Vaccines for gonorrhea: can we rise to the challenge? Front Microbiol 2:124

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhu T, McClure R, Harrison OB, Genco C, Massari P (2019) Integrated Bioinformatic Analyses and Immune Characterization of New Neisseria gonorrhoeae Vaccine Antigens Expressed during Natural Mucosal Infection. Vaccines. https://doi.org/10.3390/vaccines7040153

    Article  PubMed  PubMed Central  Google Scholar 

  • Zughaier SM, Rouquette-Loughlin CE, Shafer WM (2020) Identification of a Neisseria gonorrhoeae histone deacetylase: Epigenetic impact on host gene expression. Pathogens. https://doi.org/10.3390/pathogens9020132

    Article  PubMed  PubMed Central  Google Scholar 

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  1. Post Graduate Centre, Management and Science University, University Drive, Off Persiaran Olahraga, Section 13, 40100, Selangor, Malaysia

    Umairah Natasya Mohd Omeershffudin

  2. Faculty of Health and Life Sciences, Management and Science University, Seksyen 13, 40100, Shah Alam, Selangor, Malaysia

    Suresh Kumar

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Omeershffudin, U.N.M., Kumar, S. Emerging threat of antimicrobial resistance in Neisseria gonorrhoeae: pathogenesis, treatment challenges, and potential for vaccine development. Arch Microbiol 205, 330 (2023). https://doi.org/10.1007/s00203-023-03663-0

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