{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T20:05:48Z","timestamp":1783109148367,"version":"3.54.6"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017638","name":"Ministry of Health of the Russian Federation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017638","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Comparative whole-genome analysis was performed for <jats:italic>Neisseria gonorrhoeae<\/jats:italic> isolates belonging to the <jats:italic>Neisseria gonorrhoeae<\/jats:italic> multiantigen sequence typing (NG-MAST) types predominant worldwide \u2014 225, 1407, 2400, 2992, and 4186 \u2014 and to genogroup 807, the most common genogroup in the Russian Federation. Here, for the first time, the complete genomes of 25 <jats:italic>N. gonorrhoeae<\/jats:italic> isolates from genogroup 807 were obtained. For NG-MAST types 225, 1407, 2400, 2992, and 4186, genomes from the Pathogenwatch database were used. The phylogenetic network constructed for 150 genomes showed that the clustering according to NG-MAST type corresponded to the clustering according to genome. Comparisons of genomes of the six sequence types revealed 8-20 genes specific to each sequence type, including the loci for phase variations and genetic components of the gonococcal genetic island (GGI). NG-MAST type 2992 and 4186 isolates either lacked the GGI or carried critical mutations in genes essential for DNA secretion. In all analyzed genogroup 807 isolates, substitution of the essential <jats:italic>atlA<\/jats:italic> gene with the <jats:italic>eppA<\/jats:italic> gene was found, accompanied by a change in the <jats:italic>traG<\/jats:italic> allele, replacement of the <jats:italic>ych<\/jats:italic> gene with <jats:italic>ych1<\/jats:italic>, and the absence of the <jats:italic>exp1<\/jats:italic> gene, which is likely to result in loss of GGI functionality. For the NG-MAST type 225, 1407 and 2400 isolates, no premature stop codons or reading frameshifts were found in the genes essential for GGI function. A relationship between isolate susceptibility to ciprofloxacin, penicillin, tetracycline and the presence of lesions in GGI genes necessary for DNA secretion was established. The <jats:italic>N. gonorrhoeae<\/jats:italic> evolutionary pathways, which allow a particular sequence type to maintain long-term predominance in the population, may include changes in genes responsible for adhesion and virulence, changes in the GGI structure, preservation of genes carrying drug resistance determinants, and changes in genes associated with host adaptation or encoding enzymes of biochemical pathways.<\/jats:p>","DOI":"10.3389\/fcimb.2022.831336","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T08:50:16Z","timestamp":1645174216000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Comparative Whole-Genome Analysis of Neisseria gonorrhoeae Isolates Revealed Changes in the Gonococcal Genetic Island and Specific Genes as a Link to Antimicrobial Resistance"],"prefix":"10.3389","volume":"12","author":[{"given":"Boris","family":"Shaskolskiy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Kravtsov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya","family":"Kandinov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofya","family":"Gorshkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Kubanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Solomka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Deryabin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Dementieva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Gryadunov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftx041","article-title":"Genomic Sequencing of Neisseria gonorrhoeae to Respond to the Urgent Threat of Antimicrobial-Resistant Gonorrhea","volume":"75","author":"Abrams","year":"2017","journal-title":"Pathog. Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1080\/21505594.2020.1851940","article-title":"The Outer-Membrane Protein MafA of Neisseria meningitidis Constitutes a Novel Protein Secretion Pathway Specific for the Fratricide Protein MafB","volume":"11","author":"Arenas","year":"2020","journal-title":"Virulence"},{"key":"B3","doi-asserted-by":"publisher","first-page":"8672","DOI":"10.1021\/bi901025v","article-title":"Crystal Structure and Acyl Chain Selectivity of Escherichia coli LpxD, the N-Acyltransferase of Lipid A Biosynthesis","volume":"48","author":"Bartling","year":"2009","journal-title":"Biochemistry"},{"key":"B4","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1007\/978-3-030-18768-2_9","article-title":"Secondary Active Transporters","volume":"92","author":"Bosshart","year":"2019","journal-title":"Subcell Biochem."},{"key":"B5","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1007\/978-3-319-75241-9_13","article-title":"Secretion of Chromosomal DNA by the Neisseria gonorrhoeae Type IV Secretion System","volume":"413","author":"Callaghan","year":"2017","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e0051921","DOI":"10.1128\/IAI.00519-21","article-title":"Transcriptional and Translational Responsiveness of the Neisseria gonorrhoeae Type IV Secretion System to Conditions of Host Infections","volume":"89","author":"Callaghan","year":"2021","journal-title":"Infect. Immun."},{"key":"B7","doi-asserted-by":"publisher","first-page":"20358","DOI":"10.2807\/ese.18.03.20358-en","article-title":"Molecular Epidemiological Typing Within the European Gonococcal Antimicrobial Resistance Surveillance Programme Reveals Predominance of a Multidrug-Resistant Clone","volume":"18","author":"Chisholm","year":"2013","journal-title":"Euro Surveill."},{"key":"B8","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1128\/JCM.02589-14","article-title":"Whole-Genome Phylogenomic Heterogeneity of Neisseria gonorrhoeae Isolates With Decreased Cephalosporin Susceptibility Collected in Canada Between 1989 and 2013","volume":"53","author":"Demczuk","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1016\/S1473-3099(16)30157-8","article-title":"Whole-Genome Sequencing to Determine Transmission of Neisseria gonorrhoeae: An Observational Study","volume":"16","author":"De Silva","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"B10","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1046\/j.1365-2958.2001.02520.x","article-title":"A Variable Genetic Island Specific for Neisseria gonorrhoeae Is Involved in Providing DNA for Natural Transformation and Is Found More Often in Disseminated Infection Isolates","volume":"41","author":"Dillard","year":"2001","journal-title":"Mol. Microbiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1146\/annurev.micro.53.1.217","article-title":"DNA Uptake in Bacteria","volume":"53","author":"Dubnau","year":"1999","journal-title":"Annu. Rev. Microbiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"4590","DOI":"10.1093\/nar\/gkt1419","article-title":"A Widespread Bacteriophage Abortive Infection System Functions Through a Type IV Toxin-Antitoxin Mechanism","volume":"42","author":"Dy","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"B13","volume-title":"Molecular Typing of Neisseria gonorrhoeae \u2013 A Study of 2013 Isolates","year":"2018"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1937","DOI":"10.1093\/jac\/dkx067","article-title":"WGS to Predict Antibiotic MICs for Neisseria gonorrhoeae","volume":"72","author":"Eyre","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e806","DOI":"10.7717\/peerj.806","article-title":"Population Structure of Neisseria gonorrhoeae Based on Whole Genome Data and Its Relationship With Antibiotic Resistance","volume":"3","author":"Ezewudo","year":"2015","journal-title":"Peer J."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/691735","article-title":"Structure and Function of the Small MutS-Related Domain","volume":"2011","author":"Fukui","year":"2011","journal-title":"Mol. Biol. Int."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e108","DOI":"10.1002\/cpbi.108","article-title":"Protein Sequence Analysis Using the MPI Bioinformatics Toolkit","volume":"72","author":"Gabler","year":"2020","journal-title":"Curr. Protoc. Bioinf."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e32337","DOI":"10.1371\/journal.pone.0032337","article-title":"Origin of the Diversity in DNA Recognition Domains in Phasevarion Associated modA Genes of Pathogenic Neisseria and Haemophilus influenzae","volume":"7","author":"Gawthorne","year":"2012","journal-title":"PloS One"},{"key":"B19","doi-asserted-by":"publisher","first-page":"17596","DOI":"10.1038\/s41598-018-35750-4","article-title":"Antimicrobial Resistance Prediction and Phylogenetic Analysis of Neisseria gonorrhoeae Isolates Using the Oxford Nanopore MinION Sequencer","volume":"8","author":"Golparian","year":"2018","journal-title":"Sci. Rep."},{"key":"B20","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s12864-020-6511-6","article-title":"Genomic Evolution of Neisseria gonorrhoeae Since the Preantibiotic Era, (1928-2013): Antimicrobial Use\/Misuse Selects for Resistance and Drives Evolution","volume":"21","author":"Golparian","year":"2020","journal-title":"BMC Genomics"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.1093\/infdis\/jiw420","article-title":"Genomic Epidemiology of Gonococcal Resistance to Extended-Spectrum Cephalosporins, Macrolides, and Fluoroquinolones in the United States 2000-2013","volume":"214","author":"Grad","year":"2016","journal-title":"J. Infect. Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1111\/j.1365-2958.2005.04964.x","article-title":"Natural Transformation of Neisseria gonorrhoeae: From DNA Donation to Homologous Recombination","volume":"59","author":"Hamilton","year":"2006","journal-title":"Mol. Microbiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1111\/j.1365-2958.2005.04521.x","article-title":"Neisseria gonorrhoeae Secretes Chromosomal DNA via a Novel Type IV Secretion System","volume":"55","author":"Hamilton","year":"2005","journal-title":"Mol. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1016\/S1473-3099(18)30225-1","article-title":"Public Health Surveillance of Multidrug-Resistant Clones of Neisseria gonorrhoeae in Europe: A Genomic Survey","volume":"18","author":"Harris","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1816","DOI":"10.1093\/infdis\/jiaa002","article-title":"Neisseria gonorrhoeae Population Genomics: Use of the Gonococcal Core Genome to Improve Surveillance of Antimicrobial Resistance","volume":"222","author":"Harrison","year":"2020","journal-title":"J. Infect. Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1016\/j.jinf.2016.08.010","article-title":"Genomic Analyses of Neisseria gonorrhoeae Reveal an Association of the Gonococcal Genetic Island With Antimicrobial Resistance","volume":"73","author":"Harrison","year":"2016","journal-title":"J. Infect."},{"key":"B27","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1093\/molbev\/msj030","article-title":"Application of Phylogenetic Networks in Evolutionary Studies","volume":"23","author":"Huson","year":"2006","journal-title":"Mol. Biol. Evol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"3109","DOI":"10.1093\/jac\/dkw279","article-title":"WGS Analysis and Molecular Resistance Mechanisms of Azithromycin-Resistant (MIC >2 mg\/L) Neisseria gonorrhoeae Isolates in Europe From 2009 to 2014","volume":"71","author":"Jacobsson","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"B29","doi-asserted-by":"publisher","first-page":"88","DOI":"10.15698\/mic2015.03.194","article-title":"Characterization of the Maf Family of Polymorphic Toxins in Pathogenic Neisseria Species","volume":"2","author":"Jamet","year":"2015","journal-title":"Microb. Cell"},{"key":"B30","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1111\/mmi.12643","article-title":"The Bacterial Septal Ring Protein RlpA Is a Lytic Transglycosylase That Contributes to Rod Shape and Daughter Cell Separation in Pseudomonas aeruginosa","volume":"93","author":"Jorgenson","year":"2014","journal-title":"Mol. Microbiol."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens9110941","article-title":"Molecular Typing of Neisseria gonorrhoeae Clinical Isolates in Russia 2018-2019: A Link Between penA Alleles and NG-MAST Types","volume":"9","author":"Kandinov","year":"2020","journal-title":"Pathogens"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1666","DOI":"10.1128\/JB.02098-12","article-title":"Mating Pair Formation Homologue TraG Is a Variable Membrane Protein Essential for Contact-Independent Type IV Secretion of Chromosomal DNA by Neisseria gonorrhoeae","volume":"195","author":"Kohler","year":"2013","journal-title":"J. Bacteriol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e02024","DOI":"10.1128\/JCM.02024-18","article-title":"Summary and Trends of the Russian Gonococcal Antimicrobial Surveillance Programme 2005-2016","volume":"5","author":"Kubanov","year":"2019","journal-title":"J. Clin. Microbiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"e00574","DOI":"10.1128\/IAI.00574-16","article-title":"Inactivation of NMB0419, Encoding a Sel1-Like Repeat (SLR) Protein, in Neisseria meningitidis Is Associated With Differential Expression of Genes Belonging to the Fur Regulon and Reduced Intraepithelial Replication","volume":"85","author":"Li","year":"2017","journal-title":"Infect. Immun."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1086\/383047","article-title":"Rapid Sequence-Based Identification of Gonococcal Transmission Clusters in a Large Metropolitan Area","volume":"189","author":"Martin","year":"2004","journal-title":"J. Infect. Dis."},{"key":"B36","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/s00430-019-00651-4","article-title":"Multiresistant Neisseria gonorrhoeae: A New Threat in Second Decade of the XXI Century","volume":"209","author":"M\u0142ynarczyk-Bonikowska","year":"2020","journal-title":"Med. Microbiol. Immunol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e109613","DOI":"10.1371\/journal.pone.0109613","article-title":"Functional Analysis of the Gonococcal Genetic Island of Neisseria gonorrhoeae","volume":"9","author":"Pachulec","year":"2014","journal-title":"PloS One"},{"key":"B38","doi-asserted-by":"publisher","first-page":"3691","DOI":"10.1093\/bioinformatics\/btv421","article-title":"Roary: Rapid Large-Scale Prokaryote Pan Genome Analysis","volume":"31","author":"Page","year":"2015","journal-title":"Bioinformatics"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00061","article-title":"The Gonococcal Genetic Island and Type IV Secretion in the Pathogenic Neisseria","volume":"2","author":"Ramsey","year":"2011","journal-title":"Front. Microbiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1146\/annurev-genet-120213-092007","article-title":"The Genetics of Neisseria Species","volume":"48","author":"Rotman","year":"2014","journal-title":"Annu. Rev. Genet."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1007\/s10096-018-3296-5","article-title":"Antimicrobial Resistance and Molecular Epidemiology Using Whole-Genome Sequencing of Neisseria gonorrhoeae in Irelan","volume":"37","author":"Ryan","year":"2018","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B42","first-page":"439","article-title":"Efflux Pumps in Neisseria gonorrhoeae: Contributions to Antimicrobial Resistance and Virulence","volume-title":"Efflux-Mediated Antimicrobial Resistance in Bacteria. Mechanisms, Regulation and Clinical Implications","author":"Shafer","year":"2016"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijid.2020.01.020","article-title":"Genetic Diversity of Neisseria gonorrhoeae Multi-Antigen Sequence Types in Russia and Europe","volume":"93","author":"Shaskolskiy","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e0220339","DOI":"10.1371\/journal.pone.0220339","article-title":"Resistance of Neisseria gonorrhoeae Isolates to Beta-Lactam Antibiotics (Benzylpenicillin and Ceftriaxone) in Russia 2015-2017","volume":"14","author":"Shaskolskiy","year":"2019","journal-title":"PloS One"},{"key":"B45","doi-asserted-by":"publisher","first-page":"5","DOI":"10.24075\/brsmu.2020.009","article-title":"Comparative Phylogenetic Analysis of Neisseria gonorrhoeae Clinical Isolates in Russia, European Union, and Japan","volume":"1","author":"Shaskolskiy","year":"2020","journal-title":"Bull. RSMU"},{"key":"B46","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/S1473-3099(17)30753-3","article-title":"Discovery, Research, and Development of New Antibiotics: The WHO Priority List of Antibiotic-Resistant Bacteria and Tuberculosis","volume":"18","author":"Tacconelli","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e00231","DOI":"10.1128\/mBio.00231-11","article-title":"Natural Competence Is a Major Mechanism for Horizontal DNA Transfer in the Oral Pathogen Porphyromonas gingivalis","volume":"3","author":"Tribble","year":"2012","journal-title":"mBio"},{"key":"B48","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1186\/s12879-015-1029-2","article-title":"Current and Future Antimicrobial Treatment of Gonorrhoea - the Rapidly Evolving Neisseria gonorrhoeae Continues to Challenge","volume":"15","author":"Unemo","year":"2015","journal-title":"BMC Infect. Dis."},{"key":"B49","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/nrurol.2016.268","article-title":"Antimicrobial-Resistant Sexually Transmitted Infections: Gonorrhoea and Mycoplasma genitalium","volume":"14","author":"Unemo","year":"2017","journal-title":"Nat. Rev. Urol."},{"key":"B50","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":"B51","doi-asserted-by":"publisher","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":"B52","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00124-09","article-title":"Novel Toxin-Antitoxin System Composed of Serine Protease and AAA-ATPase Homologues Determines the High Level of Stability and Incompatibility of the Tumor-Inducing Plasmid pTiC58","volume":"191","author":"Yamamoto","year":"2009","journal-title":"J. Bacteriol."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1186\/1745-6150-7-18","article-title":"Polymorphic Toxin Systems: Comprehensive Characterization of Trafficking Modes, Processing, Mechanisms of Action, Immunity and Ecology Using Comparative Genomics","volume":"7","author":"Zhang","year":"2012","journal-title":"Biol. Direct."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.831336\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T08:50:21Z","timestamp":1645174221000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2022.831336\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,18]]},"references-count":53,"alternative-id":["10.3389\/fcimb.2022.831336"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2022.831336","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,18]]},"article-number":"831336"}}