title: Genomic analyses of Neisseria gonorrhoeae reveal an association of the gonococcal genetic island with antimicrobial resistance.
abstract: Antimicrobial resistance (AMR) threatens our ability to treat the sexually transmitted bacterial infection gonorrhoea. The increasing availability of whole genome sequence (WGS) data from Neisseria gonorrhoeae isolates, however, provides us with an opportunity in which WGS can be mined for AMR determinants.
  
  
  
  Chromosomal and plasmid genes implicated in AMR were catalogued on the PubMLST Neisseria database (http://pubmlst.org/neisseria). AMR genotypes were identified in WGS from 289 gonococci for which MICs against several antimicrobial compounds had been determined. Whole genome comparisons were undertaken using whole genome MLST (wgMLST).
  
  
  
  Clusters of isolates with distinct AMR genotypes were apparent following wgMLST analysis consistent with the occurrence of genome wide genetic variation. This included the presence of the gonococcal genetic island (GGI), a type 4 secretion system shown to increase recombination and for which possession was significantly associated with AMR to multiple antimicrobials.
  
  
  
  Evolution of the gonococcal genome occurs in response to antimicrobial selective pressure resulting in the formation of distinct N. gonorrhoeae populations evidenced by the wgMLST clusters seen here. Genomic islands offer selective advantages to host bacteria and possession of the GGI may, not only facilitate the spread of AMR in gonococcal populations, but may also confer fitness advantages.
authors: Department of Zoology, University of Oxford, Oxford, UK. Electronic address: odile.harrison@zoo.ox.ac.uk.
authors: Odile B
authors: OB
authors: Harrison
authors: Department of Zoology, University of Oxford, Oxford, UK.
authors: Marianne
authors: M
authors: Clemence
authors: Department of Medical Microbiology, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
authors: Joseph P
authors: JP
authors: Dillard
authors: Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
authors: Christoph M
authors: CM
authors: Tang
authors: Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors: David
authors: D
authors: Trees
authors: Harvard TH Chan School of Public Health, Boston, MA, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Yonatan H
authors: YH
authors: Grad
authors: Department of Zoology, University of Oxford, Oxford, UK.
authors: Martin C J
authors: MC
authors: Maiden
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002876:Chromosomes, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D044404:Genomic Islands; D023281:Genomics; D005838:Genotype; D006069:Gonorrhea / Q000453:epidemiology / Q000382:microbiology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008826:Microbial Sensitivity Tests; D058977:Molecular Sequence Annotation; D058885:Multilocus Sequence Typing; D009344:Neisseria gonorrhoeae / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D010957:Plasmids; D000069319:Type IV Secretion Systems / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D000069319:Type IV Secretion Systems
keywords: Antimicrobial resistance; Gene-by-gene annotation; Type IV secretion system; Whole-genome sequencing