title: The novel 2016 WHO Neisseria gonorrhoeae reference strains for global quality assurance of laboratory investigations: phenotypic, genetic and reference genome characterization.
abstract: Gonorrhoea and MDR Neisseria gonorrhoeae remain public health concerns globally. Enhanced, quality-assured, gonococcal antimicrobial resistance (AMR) surveillance is essential worldwide. The WHO global Gonococcal Antimicrobial Surveillance Programme (GASP) was relaunched in 2009. We describe the phenotypic, genetic and reference genome characteristics of the 2016 WHO gonococcal reference strains intended for quality assurance in the WHO global GASP, other GASPs, diagnostics and research worldwide.
  
  
  
  The 2016 WHO reference strains (n = 14) constitute the eight 2008 WHO reference strains and six novel strains. The novel strains represent low-level to high-level cephalosporin resistance, high-level azithromycin resistance and a porA mutant. All strains were comprehensively characterized for antibiogram (n = 23), serovar, prolyliminopeptidase, plasmid types, molecular AMR determinants, N. gonorrhoeae multiantigen sequence typing STs and MLST STs. Complete reference genomes were produced using single-molecule PacBio sequencing.
  
  
  
  The reference strains represented all available phenotypes, susceptible and resistant, to antimicrobials previously and currently used or considered for future use in gonorrhoea treatment. All corresponding resistance genotypes and molecular epidemiological types were described. Fully characterized, annotated and finished references genomes (n = 14) were presented.
  
  
  
  The 2016 WHO gonococcal reference strains are intended for internal and external quality assurance and quality control in laboratory investigations, particularly in the WHO global GASP and other GASPs, but also in phenotypic (e.g. culture, species determination) and molecular diagnostics, molecular AMR detection, molecular epidemiology and as fully characterized, annotated and finished reference genomes in WGS analysis, transcriptomics, proteomics and other molecular technologies and data analysis.
authors.affiliation: WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden magnus.unemo@regionorebrolan.se.
authors.forename: Magnus
authors.initials: M
authors.lastname: Unemo
authors.affiliation: WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Golparian
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridgeshire, UK.
authors.forename: Leonor
authors.initials: L
authors.lastname: Sánchez-Busó
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.|Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Grad
authors.affiliation: WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Jacobsson
authors.affiliation: Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohnishi
authors.affiliation: WHO Collaborating Centre for Sexually Transmitted Diseases, Department of Microbiology, South Eastern Area Laboratory Services, The Prince of Wales Hospital, Randwick, Sydney, Australia.
authors.forename: Monica M
authors.initials: MM
authors.lastname: Lahra
authors.affiliation: WHO Collaborating Centre for Sexually Transmitted Diseases, Department of Microbiology, South Eastern Area Laboratory Services, The Prince of Wales Hospital, Randwick, Sydney, Australia.
authors.forename: Athena
authors.initials: A
authors.lastname: Limnios
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA.
authors.forename: Aleksandra E
authors.initials: AE
authors.lastname: Sikora
authors.affiliation: Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland.
authors.forename: Teodora
authors.initials: T
authors.lastname: Wi
authors.affiliation: Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridgeshire, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D005838:Genotype; D006069:Gonorrhea / Q000382:microbiology*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000592:standards*; D058889:Molecular Typing; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D010957:Plasmids / Q000032:analysis; D011785:Quality Assurance, Health Care; D012015:Reference Standards; D065288:Serogroup
chemical_list: D000900:Anti-Bacterial Agents