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YI.4 Gonococcal Genomics Shows Impact of Recombination on Obscuring Phylogenetic Signal and Disseminating Resistance Loci
  1. Y Grad1,2,
  2. R Kirkcaldy3,
  3. J Dordel4,
  4. E Goldstein1,
  5. D Trees3,
  6. H Weinstock3,
  7. J Parkhill4,
  8. W P Hanage1,
  9. S Bentley4,5,
  10. M Lipsitch1,6
  1. 1Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States
  2. 2Division of Infectious Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States
  3. 3Centers for Disease Control and Prevention, Atlanta, GA, United States
  4. 4Wellcome Trust Sanger Institute, Hinxton, UK
  5. 5Department of Medicine, University of Cambridge, Addenbrookes Hospital, Cambridge, UK
  6. 6Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, United States

Abstract

Background Recombination plays a significant role in the plasticity of the Neisseria gonorrhoeaegenome by generating antigenic diversity and as a mechanism of spread of antibiotic resistance elements. Extensive recombination in a population can also limit inferences about phylogenetic history. Here, we investigate the impact of recombination in the study of isolates with reduced susceptibility to cefixime (cefRS; cefixime MICs ≥ 0.25 µg/ml) in the United States.

Methods We generated draught genome sequences for 242 gonococcal isolates collected by CDC’s Gonococcal Isolate Surveillance Program (GISP). These isolates comprise all 141 cefRS isolates from GISP in 2009–10 and 141 susceptible isolates matched by location, collection date, and sexual orientation of the infected individual. We predicted recombinant regions and generated a maximum likelihood phylogenetic tree from core SNPs. We performed in silico MLST and NG-MAST typing, and compared phylogenies of antibiotic resistance loci to whole genome-based phylogenies.

Results Per site r/mratios (relative likelihood that a polymorphism was introduced through recombination rather than mutation) of recent branches in the phylogenetic tree are higher and fraction of homoplasic sites much lower than for the overall tree, suggesting that extensive recombination reduces confidence in the phylogeny’s deep branches. Comparison with in silicoMLST and NG-MAST reveals that traditional typing-based phylogenetic inferences, even for recent events, are confounded by recombination. Of the 21 penA alleles in this dataset, mosaic PBP2 pattern XXXIV was the most common (present in 116/121 cefRS isolates). We find several recombination events introducing this allele into distinct lineages, and an event within the dcw gene cluster, which includes the penA allele, associated with reversion from cefRS to cefixime susceptibility.

Conclusions Genomic methods reveal the impact of recombination on phylogenetic history, spread of resistance elements, and genome evolution, and offer a superior approach to traditional typing schemes in understanding population structure and dynamics.

  • disseminating resistance loci
  • Gonococcal genomics
  • phylogenetic signal

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