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Meningococcal core and accessory phasomes vary by clonal complex.

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This summary is machine-generated.

Neisseria meningitidis phase variation influences disease potential. Analysis of 3328 genomes reveals that while the number of phase-variable genes varies, their presence co-evolves with the core genome, impacting surface antigens and vaccine development.

Keywords:
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Area of Science:

  • Microbiology
  • Genomics
  • Evolutionary Biology

Background:

  • Neisseria meningitidis exhibits phenotypic plasticity through phase-variable (PV) gene expression, a process mediated by simple sequence repeats (SSRs).
  • Different circulating N. meningitidis lineages (clonal complexes, ccs) display varying disease propensities, ranging from hypervirulent to carriage-associated.

Purpose of the Study:

  • To investigate the role of phase variation in N. meningitidis disease propensity by analyzing the phase-variable gene repertoires (phasomes) of different lineages.
  • To determine if differences in phasome content correlate with hypervirulence or carriage association in N. meningitidis.

Main Methods:

  • Analysis of 3328 N. meningitidis genomes from nine circulating clonal complexes using PhasomeIt to identify PV genes based on SSRs and homologous gene clusters.
  • Confirmation of PV gene presence, absence, and function through annotation and BLAST searches in the Neisseria PubMLST database.
  • Comparison of phasome content and core genome phylogeny between hypervirulent and carriage-associated lineages.

Main Results:

  • No significant differences in the total number of PV genes or core phasome content were found between hypervirulent and carriage lineages.
  • Individual clonal complexes showed substantial variation in PV gene numbers, with phylogenetic clustering aligning between phasome and core genome analyses, suggesting co-evolution.
  • While PV gene clusters are highly conserved (76%), SSR maintenance varies, indicating distinct evolutionary paths. Most PV genes influence surface antigens, relevant for vaccine development.

Conclusions:

  • Phase variation contributes to N. meningitidis phenotypic diversity, but differences in phasome content do not directly distinguish hypervirulent from carriage lineages.
  • Co-evolution of PV genes with the core genome is evident, with ongoing evolution of PV gene content (open pan phasomes) suggesting significant adaptive potential.
  • The influence of PV genes on surface antigens highlights their importance for understanding meningococcal pathogenesis and potential targets for future vaccine strategies.