Modelling evolutionary pathways for commensalism and hypervirulence in Neisseria meningitidis

Area of Science:

• Microbiology
• Evolutionary Biology
• Genomics

Background:

• Neisseria meningitidis, the meningococcus, causes invasive meningococcal disease (IMD) and exists as distinct clonal complexes.
• Some lineages are commensal colonizers, while others are hypervirulent and over-represented in IMD cases.

Purpose of the Study:

• To investigate the evolutionary pathways differentiating pathogenic and commensal Neisseria meningitidis lineages.
• To examine the roles of horizontally acquired genomic islands (GIs) and loss-of-function (LOF) mutations in meningococcal evolution.

Main Methods:

• Analyzed 4850 N. meningitidis genomes from the BIGSdb database.
• Identified 82 GIs and 144 frameshift loci across 11 lineages.
• Utilized a new computational tool, Phaser, to detect frameshift mutations.
• Assessed the association of GIs and LOF mutations with genetic lineage and invasiveness using the disease carriage ratio.

Main Results:

• 82 GIs were identified and associated with genetic lineage and invasiveness, but LOF mutations were not.
• Phaser identified 105 frameshift loci with statistically significant non-random distribution.
• Genomic islands were enriched for genes involved in host attachment, iron uptake, and toxin expression.

Conclusions:

• Genomic islands, not LOF mutations, appear to drive the evolution of hypervirulent Neisseria meningitidis.
• Acquisition of GIs likely enhances competition within the human nasopharynx, facilitating transition to invasive disease.
• Evolutionary pathways favor traits that increase host cell access, leading to a higher risk of IMD.