Poster Presentation BacPath 13: Molecular Analysis of Bacterial Pathogens Conference 2015

Epigenetic regulation by the ModD1 methyltransferase in N. meningitidis (#175)

Aimee Tan 1 , Dorothea Hill 2 , Benjamin L Schulz 3 , Yogitha N Srikhanta 4 , Odile Harrison 2 , Martin Maiden 2 , Michael P Jennings 1 , Kate L Seib 1
  1. Institute for Glycomics, Griffith University, Gold Coast, QLD, Australia
  2. Department of Zoology, Oxford University, Oxford, UK
  3. School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD, Australia
  4. Department of Microbiology and Immunology, University of Melbourne, Melbourne, VIC, Australia

Neisseria meningitidis strains can encode up to three independent, epigenetic, regulators, known as ModA, ModB and ModD. These proteins are phase-variable – whereby expression switches ON (protein produced) or OFF (not produced), depending on the number of DNA repeats in the open reading frame. A number of allelic variants exist for each mod gene, which differ in the DNA recognition domain sequence, and the corresponding Mod proteins mediate epigenetic regulation of different sets of genes. These phase-variable regulons are known as phasevarions, and it is hypothesised that different mod alleles (and corresponding phasevarions) may be associated with the pathogenicity of N. meningitidis strains.

The distribution and specific allele frequency of the mod genes in N. meningitidis strain collections demonstrated associations between certain mod alleles and specific clonal complexes. These clonal complexes include both hypervirulent lineages, responsible for the majority of disease worldwide, as well as those that are rarely associated with disease and more commonly isolated as strains that colonize asymptomatically. Most notably, the modD1 allele was shown to be significantly associated with hypervirulent, clonal complex 41/44 (cc41/44) strains, but was absent from all screened carriage strains. Examination of the ModD1 protein in a cc41/44 isolate (strain M4407) demonstrated it was a functional DNA methyltransferase that recognises and methylates the 5ʹ-CCm6AGC-3ʹ motif. Comparison of strains with ModD1 switched ON and OFF demonstrated differences in expression of cytoplasmic and outer membrane proteins in SWATH-MS proteomic analyses. Phenotypic analysis also indicated that strains with ModD1 ON have decreased adherence to epithelial cells and decreased survival in normal human serum. These data suggest that modD1 may affect the virulence of N. meningitidis isolates.