title: Genomic Epidemiology and Molecular Resistance Mechanisms of Azithromycin-Resistant Neisseria gonorrhoeae in Canada from 1997 to 2014.
abstract: The emergence of Neisseria gonorrhoeae strains with decreased susceptibility to cephalosporins and azithromycin (AZM) resistance (AZM(r)) represents a public health threat of untreatable gonorrhea infections. Genomic epidemiology through whole-genome sequencing was used to describe the emergence, dissemination, and spread of AZM(r) strains. The genomes of 213 AZM(r) and 23 AZM-susceptible N. gonorrhoeae isolates collected in Canada from 1989 to 2014 were sequenced. Core single nucleotide polymorphism (SNP) phylogenomic analysis resolved 246 isolates into 13 lineages. High-level AZM(r) (MICs ≥ 256 μg/ml) was found in 5 phylogenetically diverse isolates, all of which possessed the A2059G mutation (Escherichia coli numbering) in all four 23S rRNA alleles. One isolate with high-level AZM(r) collected in 2009 concurrently had decreased susceptibility to ceftriaxone (MIC = 0.125 μg/ml). An increase in the number of 23S rRNA alleles with the C2611T mutations (E. coli numbering) conferred low to moderate levels of AZM(r) (MICs = 2 to 4 and 8 to 32 μg/ml, respectively). Low-level AZM(r) was also associated with mtrR promoter mutations, including the -35A deletion and the presence of Neisseria meningitidis-like sequences. Geographic and temporal phylogenetic clustering indicates that emergent AZM(r) strains arise independently and can then rapidly expand clonally in a region through local sexual networks.
authors.affiliation: Bacteriology and Enteric Diseases Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Walter
authors.initials: W
authors.lastname: Demczuk
authors.affiliation: Bacteriology and Enteric Diseases Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Irene
authors.initials: I
authors.lastname: Martin
authors.affiliation: Bacteriology and Enteric Diseases Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Shelley
authors.initials: S
authors.lastname: Peterson
authors.affiliation: Bacteriology and Enteric Diseases Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Amrita
authors.initials: A
authors.lastname: Bharat
authors.affiliation: Science Technology Cores and Services Division, National Microbiology Laboratory, Public Health Agency of Canada, and Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Van Domselaar
authors.affiliation: Science Technology Cores and Services Division, National Microbiology Laboratory, Public Health Agency of Canada, and Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Morag
authors.initials: M
authors.lastname: Graham
authors.affiliation: Laboratoire de Santé Publique du Québec, Ste-Anne-de-Bellevue, Québec, Canada.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Lefebvre
authors.affiliation: Public Health Ontario Laboratories, Toronto, Ontario, Canada.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Allen
authors.affiliation: British Columbia Centres for Disease Control Public Health Microbiology & Reference Laboratory, Vancouver, British Columbia, Canada.
authors.forename: Linda
authors.initials: L
authors.lastname: Hoang
authors.affiliation: Provincial Laboratory for Public Health, Edmonton, Alberta, Canada.
authors.forename: Greg
authors.initials: G
authors.lastname: Tyrrell
authors.affiliation: Saskatchewan Disease Control Laboratory, Regina, Saskatchewan, Canada.
authors.forename: Greg
authors.initials: G
authors.lastname: Horsman
authors.affiliation: Cadham Provincial Laboratory, Winnipeg, Manitoba, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Wylie
authors.affiliation: Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Haldane
authors.affiliation: Centre for Communicable Diseases and Infection Control, Public Health Agency of Canada, Ottawa, Ontario, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Archibald
authors.affiliation: First Nations and Inuit Health Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: Tom
authors.initials: T
authors.lastname: Wong
authors.affiliation: Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Unemo
authors.affiliation: Bacteriology and Enteric Diseases Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada Michael.Mulvey@phac-aspc.gc.ca.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Mulvey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D002170:Canada / Q000453:epidemiology; D016000:Cluster Analysis; D005260:Female; D016680:Genome, Bacterial; D006069:Gonorrhea / Q000453:epidemiology* / Q000382:microbiology*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D017720:Molecular Epidemiology; D009154:Mutation; D009344:Neisseria gonorrhoeae / Q000145:classification* / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012338:RNA, Ribosomal, 23S; D012097:Repressor Proteins; C087450:mtrR protein, Neisseria gonorrhoeae; D017963:Azithromycin