High frequency changes in pilin glycosylation patterns of epidemic serogroup A<em> Neisseria meningitidis</em> strains in the African meningitis belt — ASN Events

High frequency changes in pilin glycosylation patterns of epidemic serogroup A Neisseria meningitidis strains in the African meningitis belt (#155)

Freda E.-C. Jen 1 , Ben L. Schulz 2 , Gerd Pluschke 3 , Michael M. Jennings 1
  1. Institute for Glycomics, Griffith University, Gold Coast, QLD, Australia
  2. School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD, Australia
  3. Swiss Tropical and Public Health Institute, Basel, Switzerland

Neisseria meningitidis is an important human pathogen that can cause rapidly progressing life threatening meningitis and sepsis in humans. The key processes that mediate the transition from harmless carriage of the bacterium in the nasopharynx (the case for the vast majority of colonised hosts) to invasive disease are largely undefined. Pili of pathogenic Neisseria are major virulence factors associated with adhesion, twitching motility, auto-aggregation, and DNA transformation. Pili of N. meningitidis are subject to several different post-translational modifications including glycosylation. Genes involved in pili glycosylation are phase-variable (high frequency, reversible on/off switching of expression). This pili-linked glycan is required for pili to optimally engage human platelet-activating factor receptor to mediate adherence to human epithelial cells.

In the meningitis belt of sub-Saharan Africa, meningococcal epidemics occur in cycles and are associated with clonal waves of N. meningitidis carriage and invasive disease. In the framework of longitudinal colonization and disease studies in Ghana and Burkina Faso, meningococcal isolates belonging to the closely related hypervirulent A:ST-5, A:ST-7 and A:ST-2859 clones have been collected from 1998-2011 during meningococcal outbreaks. A comparative whole genome sequencing study with 100 of these isolates identified the pilin glycosylation (pgl) locus as one hot spot of recombination. Frequent exchange of pgl genes in N. meningitidis by lateral gene transfer results in differences in the glycosylation patterns of pilin and of other major cell surface protein antigens. In this study, we looked at phase variation of the pgl genes of representative strains. The glycan structures resulting from different pgl alleles were determined by mass spectrometry. Our results indicate that the basal sugar is masked by various mono- or di-saccharide structures which are variable due to the phase variable expression of pgl genes. This is a strong indication for bacterial adaptation to evade host immunity.

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