Oral Presentation Society for Molecular Biology and Evolution Conference 2016

Genome-wide association study of carriage versus invasive disease in Neisseria meningitidis (#214)

Sarah G Earle 1 , Holly B Bratcher 2 , Odile B Harrison 2 , Dorothea MC Hill 2 , Paula Kriz 3 , Christoph M Tang 4 , Martin CJ Maiden 2 , Daniel J Wilson 1 5
  1. Nuffield Department of Medicine, University of Oxford, Oxford, UK
  2. Department of Zoology, University of Oxford, Oxford, UK
  3. National Reference Laboratory for Meningococcal Infections, National Institute of Public Health, Prague, Czech Republic
  4. Sir William Dunn School of Pathology, University of Oxford, Oxford, UK
  5. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

The human pathogen Neisseria meningitidis, the meningococcus, is a major cause of bacterial septicaemia and meningitis worldwide. However, N. meningitidis is principally a commensal. Although the commensal nature of the majority of meningococcal infections is well understood, the factors promoting the transition of asymptomatic carriage to invasive disease remain to be fully elucidated. Host factors such as carriage state, complement deficiencies, social behavior, and geographic location are associated with increased disease risk. Colonization with hyperinvasive meningococci is also a major risk factor for invasive disease, but the bacterial genetic mechanisms underlying invasiveness are not well understood. 

Here, we investigated the genetic basis of carriage versus invasive disease in 261 isolates of N. meningitidis by a genome-wide association study (GWAS), applying methods we adapted to bacteria to capture both lineage-associated differences and locus-specific effects on phenotype. Associations were tested between carriage versus disease and both SNPs and the presence/absence of 31bp "kmers".

We found significant associations at variants within genes involved in the synthesis of the polysaccharide capsule, a well established virulence factor and a major component contributing to the survival of the bacteria in the blood stream and cerebrospinal fluid, within possible phase variable regions, plus other regions representing potentially novel virulence factors. This has important implications for understanding virulence in N. meningitidis, and why only some strains cause disease. Association studies of this kind have the potential to provide insight into identifying virulent strains, and could further provide candidate targets to assist approaches in treating and preventing meningococcal disease.