{"entity": "researcher", "timestamp": "2026-08-09T07:11:56.851Z", "family": "Unemo", "given": "Magnus", "initials": "M", "orcid": "0000-0003-1710-2081", "affiliations": ["WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, \u00d6rebro University, \u00d6rebro, Sweden"], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/6f1494bae3b140a3a8761092e420a5de.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/6f1494bae3b140a3a8761092e420a5de"}}, "publications": [{"entity": "publication", "iuid": "2b1f93156c57480db87debbb7a3c5f02", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2b1f93156c57480db87debbb7a3c5f02.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2b1f93156c57480db87debbb7a3c5f02"}}, "title": "In silico gepotidacin target mining among 33 213 global Neisseria gonorrhoeae genomes from 1928 to 2023 combined with gepotidacin MIC testing of 22 gonococcal isolates with different GyrA and ParC substitutions.", "authors": [{"family": "David", "given": "Alexandra", "initials": "A"}, {"family": "Golparian", "given": "Daniel", "initials": "D"}, {"family": "Jacobsson", "given": "Susanne", "initials": "S"}, {"family": "Stratton", "given": "Caleb", "initials": "C"}, {"family": "Lan", "given": "Pham Thi", "initials": "PT"}, {"family": "Shimuta", "given": "Ken", "initials": "K"}, {"family": "Sonnenberg", "given": "Pam", "initials": "P"}, {"family": "Field", "given": "Nigel", "initials": "N"}, {"family": "Ohnishi", "given": "Makoto", "initials": "M"}, {"family": "Davies", "given": "Christopher", "initials": "C"}, {"family": "Unemo", "given": "Magnus", "initials": "M", "orcid": "0000-0003-1710-2081", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1494bae3b140a3a8761092e420a5de.json"}}], "type": "journal article", "published": "2024-09-03", "journal": {"title": "J. Antimicrob. Chemother.", "issn": "1460-2091", "volume": "79", "issue": "9", "pages": "2221-2226", "issn-l": "0305-7453"}, "abstract": "The novel dual-target triazaacenaphthylene, gepotidacin, recently showed promising results in its Phase III randomized controlled trial for the treatment of gonorrhoea. We investigated alterations in the gepotidacin GyrA and ParC targets in gonococci by in silico mining of publicly available global genomes (n = 33 213) and determined gepotidacin MICs in isolates with GyrA A92 alterations combined with other GyrA and/or ParC alterations.\n\nWe examined gonococcal gyrA and parC alleles available at the European Nucleotide Archive. MICs were determined using the agar dilution method (gepotidacin) or Etest (four antimicrobials). Models of DNA gyrase and topoisomerase IV were obtained from AlphaFold and used to model gepotidacin in the binding site.\n\nGyrA A92 alterations were identified in 0.24% of genomes: GyrA A92P/S/V + S91F + D95Y/A/N (0.208%), A92P + S91F (0.024%) and A92P (0.003%), but no A92T (previously associated with gepotidacin resistance) was found. ParC D86 alterations were found in 10.6% of genomes: ParC D86N/G (10.5%), D86N + S87I (0.051%), D86N + S88P (0.012%) and D86G + E91G (0.003%). One isolate had GyrA A92P + ParC D86N alterations, but remained susceptible to gepotidacin (MIC = 0.125 mg/L). No GyrA plus ParC alterations resulted in a gepotidacin MIC > 4 mg/L. Modelling of gepotidacin binding to GyrA A92/A92T/A92P suggested that gepotidacin resistance due to GyrA A92T might be linked to the formation of a new polar contact with DNA.\n\nIn silico mining of 33 213 global gonococcal genomes (isolates from 1928 to 2023) showed that A92 is highly conserved in GyrA, while alterations in D86 of ParC are common. No GyrA plus ParC alterations caused gepotidacin resistance. MIC determination and genomic surveillance of potential antimicrobial resistance determinants are imperative.", "doi": "10.1093/jac/dkae217", "pmid": "39004438", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11368423"}, {"db": "pii", "key": "7708821"}], "notes": [], "created": "2024-11-20T14:58:43.743Z", "modified": "2024-11-20T14:58:43.776Z"}, {"entity": "publication", "iuid": "af08cdee7c4e4e6d89242e17aa19f267", "links": {"self": {"href": "https://publications.scilifelab.se/publication/af08cdee7c4e4e6d89242e17aa19f267.json"}, "display": {"href": "https://publications.scilifelab.se/publication/af08cdee7c4e4e6d89242e17aa19f267"}}, "title": "The novel 2024 WHO Neisseria gonorrhoeae reference strains for global quality assurance of laboratory investigations and superseded WHO N. gonorrhoeae reference strains-phenotypic, genetic and reference genome characterization.", "authors": [{"family": "Unemo", "given": "Magnus", "initials": "M", "orcid": "0000-0003-1710-2081", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1494bae3b140a3a8761092e420a5de.json"}}, {"family": "S\u00e1nchez-Bus\u00f3", "given": "Leonor", "initials": "L"}, {"family": "Golparian", "given": "Daniel", "initials": "D"}, {"family": "Jacobsson", "given": "Susanne", "initials": "S"}, {"family": "Shimuta", "given": "Ken", "initials": "K"}, {"family": "Lan", "given": "Pham Thi", "initials": "PT"}, {"family": "Eyre", "given": "David W", "initials": "DW"}, {"family": "Cole", "given": "Michelle", "initials": "M"}, {"family": "Maatouk", "given": "Ismael", "initials": "I", "orcid": "0000-0003-1008-7413", "researcher": {"href": "https://publications.scilifelab.se/researcher/8bdc82f7504e46ea91e3343b025b1dab.json"}}, {"family": "Wi", "given": "Teodora", "initials": "T"}, {"family": "Lahra", "given": "Monica M", "initials": "MM"}], "type": "journal article", "published": "2024-08-01", "journal": {"title": "J. Antimicrob. Chemother.", "issn": "1460-2091", "volume": "79", "issue": "8", "pages": "1885-1899", "issn-l": "0305-7453"}, "abstract": "MDR and XDR Neisseria gonorrhoeae strains remain major public health concerns internationally, and quality-assured global gonococcal antimicrobial resistance (AMR) surveillance is imperative. The WHO global Gonococcal Antimicrobial Surveillance Programme (GASP) and WHO Enhanced GASP (EGASP), including metadata and WGS, are expanding internationally. We present the phenotypic, genetic and reference genome characteristics of the 2024 WHO gonococcal reference strains (n = 15) for quality assurance worldwide. All superseded WHO gonococcal reference strains (n = 14) were identically characterized.\n\nThe 2024 WHO reference strains include 11 of the 2016 WHO reference strains, which were further characterized, and four novel strains. The superseded WHO reference strains include 11 WHO reference strains previously unpublished. All strains were characterized phenotypically and genomically (single-molecule PacBio or Oxford Nanopore and Illumina sequencing).\n\nThe 2024 WHO reference strains represent all available susceptible and resistant phenotypes and genotypes for antimicrobials currently and previously used (n = 22), or considered for future use (n = 3) in gonorrhoea treatment. The novel WHO strains include internationally spreading ceftriaxone resistance, ceftriaxone resistance due to new penA mutations, ceftriaxone plus high-level azithromycin resistance and azithromycin resistance due to mosaic MtrRCDE efflux pump. AMR, serogroup, prolyliminopeptidase, genetic AMR determinants, plasmid types, molecular epidemiological types and reference genome characteristics are presented for all strains.\n\nThe 2024 WHO gonococcal reference strains are recommended for internal and external quality assurance in laboratory examinations, especially in the WHO GASP, EGASP and other GASPs, but also in phenotypic and molecular diagnostics, AMR prediction, pharmacodynamics, epidemiology, research and as complete reference genomes in WGS analysis.", "doi": "10.1093/jac/dkae176", "pmid": "38889110", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11290888"}, {"db": "pii", "key": "7695846"}], "notes": [], "created": "2024-11-20T14:58:06.821Z", "modified": "2024-11-20T14:58:06.930Z"}, {"entity": "publication", "iuid": "0fc05f7c131445c9996a87a8afeb9686", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0fc05f7c131445c9996a87a8afeb9686.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0fc05f7c131445c9996a87a8afeb9686"}}, "title": "Pharmacodynamic evaluation of ceftriaxone single-dose therapy (0.125-1 g) to eradicate ceftriaxone-susceptible and ceftriaxone-resistant Neisseria gonorrhoeae strains in a hollow fibre infection model for gonorrhoea.", "authors": [{"family": "Unemo", "given": "Magnus", "initials": "M", "orcid": "0000-0003-1710-2081", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1494bae3b140a3a8761092e420a5de.json"}}, {"family": "Golparian", "given": "Daniel", "initials": "D"}, {"family": "Oxelbark", "given": "Joakim", "initials": "J"}, {"family": "Kong", "given": "Fabian Y S", "initials": "FYS", "orcid": "0000-0002-9349-3080", "researcher": {"href": "https://publications.scilifelab.se/researcher/592aa4c01f1f459bb37fd93377d3040e.json"}}, {"family": "Brown", "given": "David", "initials": "D"}, {"family": "Louie", "given": "Arnold", "initials": "A", "orcid": "0000-0001-6227-7580", "researcher": {"href": "https://publications.scilifelab.se/researcher/e361bfdb54dd49cba340a5733c6654a2.json"}}, {"family": "Drusano", "given": "George", "initials": "G", "orcid": "0000-0001-9162-7332", "researcher": {"href": "https://publications.scilifelab.se/researcher/7c67e6f2c51d455da8c196529c719dd3.json"}}, {"family": "Jacobsson", "given": "Susanne", "initials": "S"}], "type": "journal article", "published": "2024-05-02", "journal": {"title": "J. Antimicrob. Chemother.", "issn": "1460-2091", "volume": "79", "issue": "5", "pages": "1006-1013", "issn-l": "0305-7453"}, "abstract": "Antimicrobial resistance in Neisseria gonorrhoeae is threatening the gonorrhoea treatment, and optimizations of the current ceftriaxone-treatment regimens are crucial. We evaluated the pharmacodynamics of ceftriaxone single-dose therapy (0.125-1 g) against ceftriaxone-susceptible and ceftriaxone-resistant gonococcal strains, based on EUCAST ceftriaxone-resistance breakpoint (MIC > 0.125 mg/L), in our hollow fibre infection model (HFIM) for gonorrhoea.\n\nGonococcal strains examined were WHO F (ceftriaxone-susceptible, MIC < 0.002 mg/L), R (ceftriaxone-resistant, MIC = 0.5 mg/L), Z (ceftriaxone-resistant, MIC = 0.5 mg/L) and X (ceftriaxone-resistant, MIC = 2 mg/L). Dose-range HFIM 7 day experiments simulating ceftriaxone 0.125-1 g single-dose intramuscular regimens were conducted.\n\nCeftriaxone 0.125-1 g single-dose treatments rapidly eradicated WHO F (wild-type ceftriaxone MIC). Ceftriaxone 0.5 and 1 g treatments, based on ceftriaxone human plasma pharmacokinetic parameters, eradicated most ceftriaxone-resistant gonococcal strains (WHO R and Z), but ceftriaxone 0.5 g failed to eradicate WHO X (high-level ceftriaxone resistance). When simulating oropharyngeal gonorrhoea, ceftriaxone 0.5 g failed to eradicate all the ceftriaxone-resistant strains, while ceftriaxone 1 g eradicated WHO R and Z (low-level ceftriaxone resistance) but failed to eradicate WHO X (high-level ceftriaxone resistance). No ceftriaxone-resistant mutants were selected using any ceftriaxone treatments.\n\nCeftriaxone 1 g single-dose intramuscularly cure most of the anogenital and oropharyngeal gonorrhoea cases caused by the currently internationally spreading ceftriaxone-resistant gonococcal strains, which should be further confirmed clinically. A ceftriaxone 1 g dose (\u00b1azithromycin 2 g) should be recommended for first-line empiric gonorrhoea treatment. This will buy countries some time until novel antimicrobials are licensed. Using ceftriaxone 1 g gonorrhoea treatment, the EUCAST ceftriaxone-resistance breakpoint is too low.", "doi": "10.1093/jac/dkae063", "pmid": "38497988", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "7630705"}], "notes": [], "created": "2024-11-20T14:55:40.522Z", "modified": "2024-11-20T14:55:41.289Z"}, {"entity": "publication", "iuid": "230c73a25d9e44ad8a846e16f341182a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/230c73a25d9e44ad8a846e16f341182a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/230c73a25d9e44ad8a846e16f341182a"}}, "title": "Recent dynamics in Neisseria gonorrhoeae genomic epidemiology in Brazil: antimicrobial resistance and genomic lineages in 2017-20 compared to 2015-16.", "authors": [{"family": "Golparian", "given": "Daniel", "initials": "D"}, {"family": "Bazzo", "given": "Maria Luiza", "initials": "ML"}, {"family": "Ahlstrand", "given": "Josefine", "initials": "J"}, {"family": "Sch\u00f6rner", "given": "Marcos Andr\u00e9", "initials": "MA"}, {"family": "Gaspar", "given": "Pamela Cristina", "initials": "PC"}, {"family": "de Melo Machado", "given": "Hanalydia", "initials": "H"}, {"family": "Martins", "given": "J\u00e9ssica Motta", "initials": "JM"}, {"family": "Bigolin", "given": "Alisson", "initials": "A"}, {"family": "Ramos", "given": "Mauro Cunha", "initials": "MC"}, {"family": "Ferreira", "given": "William Antunes", "initials": "WA"}, {"family": "Pereira", "given": "Gerson Fernando Mendes", "initials": "GFM"}, {"family": "Miranda", "given": "Angelica Espinosa", "initials": "AE"}, {"family": "Unemo", "given": "Magnus", "initials": "M", "orcid": "0000-0003-1710-2081", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1494bae3b140a3a8761092e420a5de.json"}}, {"family": "Brazilian-GASP Network", "given": "", "initials": ""}], "type": "journal article", "published": "2024-05-02", "journal": {"title": "J. Antimicrob. Chemother.", "issn": "1460-2091", "volume": "79", "issue": "5", "pages": "1081-1092", "issn-l": "0305-7453"}, "abstract": "Regular quality-assured WGS with antimicrobial resistance (AMR) and epidemiological data of patients is imperative to elucidate the shifting gonorrhoea epidemiology, nationally and internationally. We describe the dynamics of the gonococcal population in 11 cities in Brazil between 2017 and 2020 and elucidate emerging and disappearing gonococcal lineages associated with AMR, compare to Brazilian WGS and AMR data from 2015 to 2016, and explain recent changes in gonococcal AMR and gonorrhoea epidemiology.\n\nWGS was performed using Illumina NextSeq 550 and genomes of 623 gonococcal isolates were used for downstream analysis. Molecular typing and AMR determinants were obtained and links between genomic lineages and AMR (determined by agar dilution/Etest) examined.\n\nAzithromycin resistance (15.6%, 97/623) had substantially increased and was mainly explained by clonal expansions of strains with 23S rRNA C2611T (mostly NG-STAR CC124) and mtr mosaics (mostly NG-STAR CC63, MLST ST9363). Resistance to ceftriaxone and cefixime remained at the same levels as in 2015-16, i.e. at 0% and 0.2% (1/623), respectively. Regarding novel gonorrhoea treatments, no known zoliflodacin-resistance gyrB mutations or gepotidacin-resistance gyrA mutations were found. Genomic lineages and sublineages showed a phylogenomic shift from sublineage A5 to sublineages A1-A4, while isolates within lineage B remained diverse in Brazil.\n\nAzithromycin resistance, mainly caused by 23S rRNA C2611T and mtrD mosaics/semi-mosaics, had substantially increased in Brazil. This mostly low-level azithromycin resistance may threaten the recommended ceftriaxone-azithromycin therapy, but the lack of ceftriaxone resistance is encouraging. Enhanced gonococcal AMR surveillance, including WGS, is imperative in Brazil and other Latin American and Caribbean countries.", "doi": "10.1093/jac/dkae075", "pmid": "38517452", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "7633595"}], "notes": [], "created": "2024-11-20T14:56:51.940Z", "modified": "2024-11-20T14:56:51.951Z"}, {"entity": "publication", "iuid": "efcf93f6fd1f41edace4d1a4948a14f7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/efcf93f6fd1f41edace4d1a4948a14f7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/efcf93f6fd1f41edace4d1a4948a14f7"}}, "title": "Complete reference genomes of two ceftriaxone-resistant Neisseria gonorrhoeae strains identified in routine surveillance in Bangkok, Thailand, using Nanopore Q20+ chemistry, VolTRAX V2b, and Illumina sequencing.", "authors": [{"family": "Sangprasert", "given": "Pongsathorn", "initials": "P"}, {"family": "Golparian", "given": "Daniel", "initials": "D"}, {"family": "Paopang", "given": "Porntip", "initials": "P"}, {"family": "Girdthep", "given": "Natnaree", "initials": "N"}, {"family": "Lawung", "given": "Ratana", "initials": "R"}, {"family": "Gopinath", "given": "Deyer", "initials": "D"}, {"family": "Thammawijaya", "given": "Panithee", "initials": "P"}, {"family": "Kittiyaowanarn", "given": "Rossaphorn", "initials": "R"}, {"family": "Unemo", "given": "Magnus", "initials": "M", "orcid": "0000-0003-1710-2081", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1494bae3b140a3a8761092e420a5de.json"}}], "type": "journal article", "published": "2024-03-12", "journal": {"title": "Microbiol Resour Announc", "issn": "2576-098X", "volume": "13", "issue": "3", "pages": "e0123123", "issn-l": "2576-098X"}, "abstract": "Ceftriaxone-resistant Neisseria gonorrhoeae strains, mostly associated with Asia, threaten gonorrhea treatment. We report the reference genomes of two ceftriaxone-resistant isolates found in routine surveillance in Bangkok, Thailand. The genomes belonged to the more antimicrobial-susceptible genomic lineage B, illustrating that both ceftriaxone-resistant strains and the mosaic penA-60.001 ceftriaxone-resistance determinant are spreading.", "doi": "10.1128/mra.01231-23", "pmid": "38299807", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10927671"}], "notes": [], "created": "2024-11-20T14:55:00.961Z", "modified": "2024-11-20T14:55:01.126Z"}, {"entity": "publication", "iuid": "b1baf91c64c04ba1a7e8409f28c55fa6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b1baf91c64c04ba1a7e8409f28c55fa6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b1baf91c64c04ba1a7e8409f28c55fa6"}}, "title": "Genomic surveillance and antimicrobial resistance determinants in Neisseria gonorrhoeae isolates from Uganda, Malawi and South Africa, 2015-20.", "authors": [{"family": "Kakooza", "given": "Francis", "initials": "F"}, {"family": "Golparian", "given": "Daniel", "initials": "D"}, {"family": "Matoga", "given": "Mitch", "initials": "M", "orcid": "0000-0002-6542-8193", "researcher": {"href": "https://publications.scilifelab.se/researcher/543841792b5e4b0292e5078e30956bac.json"}}, {"family": "Maseko", "given": "Venessa", "initials": "V"}, {"family": "Lamorde", "given": "Mohammed", "initials": "M"}, {"family": "Krysiak", "given": "Robert", "initials": "R"}, {"family": "Manabe", "given": "Yuka C", "initials": "YC"}, {"family": "Chen", "given": "Jane S", "initials": "JS"}, {"family": "Kularatne", "given": "Ranmini", "initials": "R"}, {"family": "Jacobsson", "given": "Susanne", "initials": "S"}, {"family": "Godreuil", "given": "Sylvain", "initials": "S"}, {"family": "Hoffman", "given": "Irving", "initials": "I"}, {"family": "Bercot", "given": "Beatrice", "initials": "B", "orcid": "0000-0003-1603-3635", "researcher": {"href": "https://publications.scilifelab.se/researcher/d24554fac15140dfa03cbe50b3291501.json"}}, {"family": "Wi", "given": "Teodora", "initials": "T"}, {"family": "Unemo", "given": "Magnus", "initials": "M", "orcid": "0000-0003-1710-2081", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1494bae3b140a3a8761092e420a5de.json"}}], "type": "journal article", "published": "2023-08-02", "journal": {"title": "J. Antimicrob. Chemother.", "issn": "1460-2091", "volume": "78", "issue": "8", "pages": "1982-1991", "issn-l": "0305-7453"}, "abstract": "Global antimicrobial resistance (AMR) surveillance in Neisseria gonorrhoeae is essential. In 2017-18, only five (10.6%) countries in the WHO African Region reported to the WHO Global Gonococcal Antimicrobial Surveillance Programme (WHO GASP). Genomics enhances our understanding of gonococcal populations nationally and internationally, including AMR strain transmission; however, genomic studies from Africa are extremely scarce. We describe the gonococcal genomic lineages/sublineages, including AMR determinants, and baseline genomic diversity among strains in Uganda, Malawi and South Africa, 2015-20, and compare with sequences from Kenya and Burkina Faso.\n\nGonococcal isolates cultured in Uganda (n = 433), Malawi (n = 154) and South Africa (n = 99) in 2015-20 were genome-sequenced. MICs were determined using ETEST. Sequences of isolates from Kenya (n = 159), Burkina Faso (n = 52) and the 2016 WHO reference strains (n = 14) were included in the analysis.\n\nResistance to ciprofloxacin was high in all countries (57.1%-100%). All isolates were susceptible to ceftriaxone, cefixime and spectinomycin, and 99.9% were susceptible to azithromycin. AMR determinants for ciprofloxacin, benzylpenicillin and tetracycline were common, but rare for cephalosporins and azithromycin. Most isolates belonged to the more antimicrobial-susceptible lineage B (n = 780) compared with the AMR lineage A (n = 141), and limited geographical phylogenomic signal was observed.\n\nWe report the first multi-country gonococcal genomic comparison from Africa, which will support the WHO GASP and WHO enhanced GASP (EGASP). The high prevalence of resistance to ciprofloxacin (and empirical use continues), tetracycline and benzylpenicillin, and the emerging resistance determinants for azithromycin show it is imperative to strengthen the gonococcal AMR surveillance, ideally including genomics, in African countries.", "doi": "10.1093/jac/dkad193", "pmid": "37352017", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "7205832"}], "notes": [], "created": "2023-09-25T13:37:50.394Z", "modified": "2023-09-25T13:37:50.518Z"}, {"entity": "publication", "iuid": "1a8ae2ebc9314bf38487740c1fe1f64b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1a8ae2ebc9314bf38487740c1fe1f64b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1a8ae2ebc9314bf38487740c1fe1f64b"}}, "title": "High-level in vitro resistance to gentamicin acquired in a stepwise manner in Neisseria gonorrhoeae.", "authors": [{"family": "Golparian", "given": "Daniel", "initials": "D"}, {"family": "Jacobsson", "given": "Susanne", "initials": "S"}, {"family": "Holley", "given": "Concerta L", "initials": "CL"}, {"family": "Shafer", "given": "William M", "initials": "WM"}, {"family": "Unemo", "given": "Magnus", "initials": "M", "orcid": "0000-0003-1710-2081", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1494bae3b140a3a8761092e420a5de.json"}}], "type": "journal article", "published": "2023-07-05", "journal": {"title": "J. Antimicrob. Chemother.", "issn": "1460-2091", "volume": "78", "issue": "7", "pages": "1769-1778", "issn-l": "0305-7453"}, "abstract": "Gentamicin is used in several alternative treatments for gonorrhoea. Verified clinical Neisseria gonorrhoeae isolates with gentamicin resistance are mainly lacking and understanding the mechanisms for gonococcal gentamicin resistance is imperative. We selected gentamicin resistance in gonococci in vitro, identified the novel gentamicin-resistance mutations, and examined the biofitness of a high-level gentamicin-resistant mutant.\n\nLow- and high-level gentamicin resistance was selected in WHO X (gentamicin MIC = 4 mg/L) on gentamicin-gradient agar plates. Selected mutants were whole-genome sequenced. Potential gentamicin-resistance fusA mutations were transformed into WT strains to verify their impact on gentamicin MICs. The biofitness of high-level gentamicin-resistant mutants was examined using a competitive assay in a hollow-fibre infection model.\n\nWHO X mutants with gentamicin MICs of up to 128 mg/L were selected. Primarily selected fusA mutations were further investigated, and fusAR635L and fusAM520I + R635L were particularly interesting. Different mutations in fusA and ubiM were found in low-level gentamicin-resistant mutants, while fusAM520I was associated with high-level gentamicin resistance. Protein structure predictions showed that fusAM520I is located in domain IV of the elongation factor-G (EF-G). The high-level gentamicin-resistant WHO X mutant was outcompeted by the gentamicin-susceptible WHO X parental strain, suggesting lower biofitness.\n\nWe describe the first high-level gentamicin-resistant gonococcal isolate (MIC = 128 mg/L), which was selected in vitro through experimental evolution. The most substantial increases of the gentamicin MICs were caused by mutations in fusA (G1560A and G1904T encoding EF-G M520I and R635L, respectively) and ubiM (D186N). The high-level gentamicin-resistant N. gonorrhoeae mutant showed impaired biofitness.", "doi": "10.1093/jac/dkad168", "pmid": "37253051", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "7186569"}, {"db": "pmc", "key": "PMC10517096"}], "notes": [], "created": "2023-09-25T13:38:18.708Z", "modified": "2023-09-25T13:38:18.719Z"}, {"entity": "publication", "iuid": "d0953f14f20e43729090b5ac6bf8c495", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d0953f14f20e43729090b5ac6bf8c495.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d0953f14f20e43729090b5ac6bf8c495"}}, "title": "Complete Reference Genome Sequence of the Clinical Neisseria gonorrhoeae Strain H035, with Resistance to the Novel Antimicrobial Zoliflodacin, Identified in Japan in 2000.", "authors": [{"family": "Golparian", "given": "Daniel", "initials": "D"}, {"family": "Jacobsson", "given": "Susanne", "initials": "S"}, {"family": "Ohnishi", "given": "Makoto", "initials": "M"}, {"family": "Unemo", "given": "Magnus", "initials": "M", "orcid": "0000-0003-1710-2081", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1494bae3b140a3a8761092e420a5de.json"}}], "type": "journal article", "published": "2023-03-16", "journal": {"title": "Microbiol Resour Announc", "issn": "2576-098X", "volume": "12", "issue": "3", "pages": "e0113022", "issn-l": "2576-098X"}, "abstract": "Zoliflodacin is a promising novel antimicrobial in clinical development for treatment of gonorrhea; currently, it is in a global phase 3 randomized controlled clinical trial. High activity against global Neisseria gonorrhoeae strains has been shown. We present the complete reference genome of the zoliflodacin-resistant strain H035, which was identified in Japan in 2000.", "doi": "10.1128/mra.01130-22", "pmid": "36853044", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10019152"}], "notes": [], "created": "2023-09-25T13:37:13.886Z", "modified": "2023-09-25T13:37:13.965Z"}, {"entity": "publication", "iuid": "610bae916a864515b21c96ba3f19f321", "links": {"self": {"href": "https://publications.scilifelab.se/publication/610bae916a864515b21c96ba3f19f321.json"}, "display": {"href": "https://publications.scilifelab.se/publication/610bae916a864515b21c96ba3f19f321"}}, "title": "GyrB in silico mining in 27 151 global gonococcal genomes from 1928-2021 combined with zoliflodacin in vitro testing of 71 international gonococcal isolates with different GyrB, ParC and ParE substitutions confirms high susceptibility.", "authors": [{"family": "Golparian", "given": "Daniel", "initials": "D"}, {"family": "Jacobsson", "given": "Susanne", "initials": "S"}, {"family": "S\u00e1nchez-Bus\u00f3", "given": "Leonor", "initials": "L"}, {"family": "Bazzo", "given": "Maria Luiza", "initials": "ML"}, {"family": "Lan", "given": "Pham Thi", "initials": "PT"}, {"family": "Galarza", "given": "Patricia", "initials": "P"}, {"family": "Ohnishi", "given": "Makoto", "initials": "M"}, {"family": "Unemo", "given": "Magnus", "initials": "M", "orcid": "0000-0003-1710-2081", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1494bae3b140a3a8761092e420a5de.json"}}], "type": "journal article", "published": "2022-10-29", "journal": {"title": "J. Antimicrob. Chemother.", "issn": "1460-2091", "issn-l": "0305-7453"}, "abstract": "Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global threat and novel treatment alternatives are imperative. Herein, susceptibility to the novel antimicrobial zoliflodacin, currently in a global Phase 3 randomized controlled clinical trial for gonorrhoea treatment, was investigated by screening for zoliflodacin GyrB target mutations in publicly available gonococcal genomes and, where feasible, determination of the associated zoliflodacin MIC.\n\nThe European Nucleotide Archive was queried using the search term 'Taxon: 485'. DNA sequences from 27 151 gonococcal isolates were analysed and gyrB, gyrA, parC and parE alleles characterized.\n\nGyrB amino acid alterations were rare (97.0% of isolates had a wild-type GyrB sequence). GyrB V470L (2.7% of isolates) was the most prevalent alteration, followed by S467N (0.12%), N. meningitidis GyrB (0.092%), V470I (0.059%), Q468R/P (0.015%), A466T (0.0074%), L425I + L465I (0.0037%), L465I (0.0037%), G482S (0.0037%) and D429V (0.0037%). Only one isolate (0.0037%) carried a substitution in a resistance-associated GyrB codon (D429V), resulting in a zoliflodacin MIC of 8 mg/L. None of the other detected gyrB, gyrA, parC or parE mutations caused a zoliflodacin MIC outside the wild-type MIC distribution.\n\nThe zoliflodacin target GyrB was highly conserved among 27 151 global gonococcal isolates cultured in 1928-2021. The single zoliflodacin-resistant clinical isolate (0.0037%) was cultured from a male patient in Japan in 2000. Evidently, this strain has not clonally expanded nor has the gyrB zoliflodacin-resistance mutation disseminated through horizontal gene transfer to other strains. Phenotypic and genomic surveillance, including gyrB mutations, of zoliflodacin susceptibility are imperative.", "doi": "10.1093/jac/dkac366", "pmid": "36308328", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "6779860"}], "notes": [], "created": "2022-11-08T08:00:26.029Z", "modified": "2022-11-08T08:00:26.053Z"}, {"entity": "publication", "iuid": "9f292637331b4d32979914e0da59f064", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9f292637331b4d32979914e0da59f064.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9f292637331b4d32979914e0da59f064"}}, "title": "Complete Reference Genome Sequence of the Extensively Drug-Resistant Strain Neisseria gonorrhoeae AT159, with Ceftriaxone Resistance and High-Level Azithromycin Resistance, Using Nanopore Q20+ Chemistry and Illumina Sequencing.", "authors": [{"family": "Golparian", "given": "Daniel", "initials": "D"}, {"family": "Pleininger", "given": "Sonja", "initials": "S"}, {"family": "Jacobsson", "given": "Susanne", "initials": "S"}, {"family": "Indra", "given": "Alexander", "initials": "A"}, {"family": "Unemo", "given": "Magnus", "initials": "M", "orcid": "0000-0003-1710-2081", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1494bae3b140a3a8761092e420a5de.json"}}], "type": "journal article", "published": "2022-09-15", "journal": {"title": "Microbiol Resour Announc", "issn": "2576-098X", "volume": "11", "issue": "9", "pages": "e0074422", "issn-l": "2576-098X"}, "abstract": "Extensively drug-resistant Neisseria gonorrhoeae (XDR-NG) strains with resistance to the last remaining first-line treatments (ceftriaxone monotherapy or combined with azithromycin) represent the emerging threat of untreatable gonorrhea. We present the complete reference genome sequence of the XDR-NG strain AT159, with ceftriaxone and high-level azithromycin resistance, from Austria.", "doi": "10.1128/mra.00744-22", "pmid": "36005764", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC9476915"}], "notes": [], "created": "2022-11-08T08:00:06.914Z", "modified": "2022-11-08T08:00:06.938Z"}, {"entity": "publication", "iuid": "016fc8c9254a4755a39278991c90e838", "links": {"self": {"href": "https://publications.scilifelab.se/publication/016fc8c9254a4755a39278991c90e838.json"}, "display": {"href": "https://publications.scilifelab.se/publication/016fc8c9254a4755a39278991c90e838"}}, "title": "Genomic surveillance and antimicrobial resistance in Neisseria gonorrhoeae isolates in Bangkok, Thailand in 2018.", "authors": [{"family": "Golparian", "given": "Daniel", "initials": "D"}, {"family": "Kittiyaowamarn", "given": "Rossaphorn", "initials": "R"}, {"family": "Paopang", "given": "Porntip", "initials": "P"}, {"family": "Sangprasert", "given": "Pongsathorn", "initials": "P"}, {"family": "Sirivongrangson", "given": "Pachara", "initials": "P"}, {"family": "Franceschi", "given": "Francois", "initials": "F"}, {"family": "Jacobsson", "given": "Susanne", "initials": "S"}, {"family": "Wi", "given": "Teodora", "initials": "T"}, {"family": "Unemo", "given": "Magnus", "initials": "M", "orcid": "0000-0003-1710-2081", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1494bae3b140a3a8761092e420a5de.json"}}], "type": "journal article", "published": "2022-07-28", "journal": {"title": "J. Antimicrob. Chemother.", "issn": "1460-2091", "volume": "77", "issue": "8", "pages": "2171-2182", "issn-l": "0305-7453"}, "abstract": "Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a substantial global public health problem. Gonococcal infections acquired in or from Asia represent most verified ceftriaxone treatment failures, and several ceftriaxone-resistant strains have emerged in Asia and subsequently spread globally. Additionally, in Thailand the gonorrhoea incidence remains high. Herein, we investigate the genomic diversity, AMR and AMR determinants in gonococcal isolates cultured in 2018 in Bangkok, Thailand.\n\nGonococcal isolates from males (n = 37) and females (n = 62) were examined by Etest and WGS. AMR determinants and molecular epidemiological STs were characterized. For phylogenomic comparison, raw sequence data were included from China (432 isolates), Japan (n = 270), Vietnam (n = 229), Thailand (n = 3), a global dataset (n = 12 440) and the 2016 WHO reference strains plus WHO Q (n = 15).\n\nIn total, 88, 66 and 41 different NG-MAST, NG-STAR and MLST STs, respectively, and 31 different NG-STAR clonal complexes were found. A remarkably high frequency (88%) of \u03b2-lactamase TEM genes was detected and two novel TEM alleles were found. The phylogenomic analysis divided the isolates into the previously described lineages A and B, with a large proportion of Thai isolates belonging to the novel sublineage A3.\n\nWe describe the first molecular epidemiological study using WGS on gonococcal isolates from Thailand. The high prevalence of AMR and AMR determinants for ciprofloxacin, tetracycline and benzylpenicillin, and some strains belonging to clones/clades especially in sublineage A2 that are prone to develop resistance to extended-spectrum cephalosporins (ESCs) and azithromycin, should prompt continued and strengthened AMR surveillance, including WGS, of N. gonorrhoeae in Thailand.", "doi": "10.1093/jac/dkac158", "pmid": "35542983", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "6583486"}], "notes": [], "created": "2022-11-08T07:59:31.161Z", "modified": "2022-11-08T07:59:31.167Z"}, {"entity": "publication", "iuid": "b3a44e9303844b0e8fdb8f107fe28a22", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b3a44e9303844b0e8fdb8f107fe28a22.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b3a44e9303844b0e8fdb8f107fe28a22"}}, "title": "Genomic epidemiology of Neisseria gonorrhoeae elucidating the gonococcal antimicrobial resistance and lineages/sublineages across Brazil, 2015-16.", "authors": [{"family": "Golparian", "given": "Daniel", "initials": "D"}, {"family": "Bazzo", "given": "Maria Luiza", "initials": "ML"}, {"family": "Golfetto", "given": "Lisl\u00e9ia", "initials": "L"}, {"family": "Gaspar", "given": "Pamela Cristina", "initials": "PC"}, {"family": "Sch\u00f6rner", "given": "Marcos Andr\u00e9", "initials": "MA"}, {"family": "Schwartz Benzaken", "given": "Adele", "initials": "A"}, {"family": "Ramos", "given": "Mauro Cunha", "initials": "MC"}, {"family": "Ferreira", "given": "William Antunes", "initials": "WA"}, {"family": "Alonso Neto", "given": "Jos\u00e9 Boullosa", "initials": "JB"}, {"family": "Mendes Pereira", "given": "Gerson Fernando", "initials": "GF"}, {"family": "Unemo", "given": "Magnus", "initials": "M", "orcid": "0000-0003-1710-2081", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1494bae3b140a3a8761092e420a5de.json"}}, {"family": "Brazilian-GASP Network", "given": "", "initials": ""}], "type": "journal article", "published": "2020-11-01", "journal": {"title": "J. Antimicrob. Chemother.", "issn": "1460-2091", "issn-l": "0305-7453", "volume": "75", "issue": "11", "pages": "3163-3172"}, "abstract": "Neisseria gonorrhoeae antimicrobial resistance (AMR) surveillance is imperative internationally, but only eight (22.9%) countries in the WHO Region of the Americas reported complete AMR data to the WHO Global Gonococcal Antimicrobial Surveillance Program (WHO GASP) in 2016. Genomic studies are ideal for enhanced understanding of gonococcal populations, including the spread of AMR strains. To elucidate the circulating gonococcal lineages/sublineages, including their AMR determinants, and the baseline genomic diversity among gonococcal strains in Brazil, we conducted WGS on 548 isolates obtained in 2015-16 across all five macroregions in Brazil.\r\n\r\nA total of 548 gonococcal isolates cultured across Brazil in 2015-16 were genome sequenced. AMR was determined using agar dilution and/or Etest. Genome sequences of isolates from Argentina (n = 158) and the 2016 WHO reference strains (n = 14) were included in the analysis.\r\n\r\nWe found 302, 68 and 214 different NG-MAST, MLST and NG-STAR STs, respectively. The phylogenomic analysis identified one main antimicrobial-susceptible lineage and one AMR lineage, which was divided into two sublineages with different AMR profiles. Determination of NG-STAR networks of clonal complexes was shown as a new and valuable molecular epidemiological analysis. Several novel mosaic mtrD (and mtrR and mtrE) variants associated with azithromycin resistance were identified.\r\n\r\nWe describe the first genomic baseline data to support the Brazilian GASP. The high prevalence of resistance to ciprofloxacin, tetracycline and benzylpenicillin, and the high number of isolates with mosaic penA and azithromycin resistance mutations, should prompt continued and strengthened AMR surveillance, including WGS, of N. gonorrhoeae in Brazil.", "doi": "10.1093/jac/dkaa318", "pmid": "32785692", "labels": {"Clinical Genomics \u00d6rebro": "Technology development", "Clinical Genomics": "Technology development"}, "xrefs": [{"db": "pii", "key": "5891806"}], "notes": [], "created": "2020-11-27T14:02:26.079Z", "modified": "2021-12-08T12:30:15.933Z"}, {"entity": "publication", "iuid": "d5a875da3329432092ef2545fdf51dfd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d5a875da3329432092ef2545fdf51dfd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d5a875da3329432092ef2545fdf51dfd"}}, "title": "Genomic analysis and antimicrobial resistance of Neisseria gonorrhoeae isolates from Vietnam in 2011 and 2015-16.", "authors": [{"family": "Lan", "given": "Pham Thi", "initials": "PT"}, {"family": "Golparian", "given": "Daniel", "initials": "D"}, {"family": "Ringlander", "given": "Johan", "initials": "J"}, {"family": "Van Hung", "given": "Le", "initials": "L"}, {"family": "Van Thuong", "given": "Nguyen", "initials": "N"}, {"family": "Unemo", "given": "Magnus", "initials": "M", "orcid": "0000-0003-1710-2081", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1494bae3b140a3a8761092e420a5de.json"}}], "type": "journal article", "published": "2020-06-01", "journal": {"title": "J. Antimicrob. Chemother.", "issn": "1460-2091", "issn-l": "0305-7453", "volume": "75", "issue": "6", "pages": "1432-1438"}, "abstract": "Antimicrobial resistance (AMR) in Neisseria gonorrhoeae, compromising gonorrhoea treatment, is a threat to reproductive health globally. South-East and East Asia have been major sources of emergence and subsequent international spread of AMR gonococcal strains during recent decades. We investigated gonococcal isolates from 2011 and 2015-16 in Vietnam using AMR testing, WGS and detection of AMR determinants.\r\n\r\nTwo hundred and twenty-nine gonococcal isolates cultured in 2015-16 (n = 121) and 2011 (n = 108) in Vietnam were examined. AMR testing was performed using Etest and WGS with Illumina MiSeq.\r\n\r\nResistance among the 2015-16 isolates was as follows: ciprofloxacin, 100%; tetracycline, 79%; benzylpenicillin, 50%; cefixime, 15%; ceftriaxone, 1%; spectinomycin, 0%; and 5% were non-WT to azithromycin. Eighteen (15%) isolates were MDR. The MIC range for gentamicin was 2-8 mg/L. Among the 2015-16 isolates, 27% (n = 33) contained a mosaic penA allele, while no isolates had a mosaic penA allele in 2011. Phylogenomic analysis revealed introduction after 2011 of two mosaic penA-containing clones (penA-10.001 and penA-34.001), which were related to cefixime-resistant strains spreading in Japan and Europe, and a minor clade (eight isolates) relatively similar to the XDR strain WHO Q.\r\n\r\nFrom 2011 to 2015-16, resistance in gonococci from Vietnam increased to all currently and previously used antimicrobials except ceftriaxone, spectinomycin and tetracycline. Two mosaic penA-containing clones were introduced after 2011, explaining the increased cefixime resistance. Significantly increased AMR surveillance, antimicrobial stewardship and use of WGS for molecular epidemiology and AMR prediction for gonococcal isolates in Vietnam and other Asian countries are crucial.", "doi": "10.1093/jac/dkaa040", "pmid": "32068837", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "5740025"}, {"db": "pmc", "key": "PMC7382555"}], "notes": [], "created": "2020-11-27T14:03:55.802Z", "modified": "2021-12-08T12:31:02.326Z"}]}