Point mutation in meningococcal por A gene associated with increased endemic disease

B T McGuinness1, I N Clarke, P R Lambden

  • 1Department of Microbiology, University of Southampton Medical School, UK.

PubMed

Insights

A mutation in the porA gene of Neisseria meningitidis alters the P1.16 epitope, impacting antibody recognition and complement-mediated killing. This altered strain (P1.16b) is prevalent in England and Wales.

Area of Science:

  • Microbiology
  • Immunology
  • Genetics

Background:

  • Neisseria meningitidis causes bacterial meningitis.
  • The porA gene encodes the class 1 outer membrane protein, crucial for antigenic specificity.
  • Meningococcal serogroup B, subtype P1.7,16, is a significant cause of infection.

Purpose of the Study:

  • To clone and sequence the porA gene from a clinical isolate of Neisseria meningitidis (B:15:P1.7,16).
  • To investigate the genetic basis of altered antigenic specificity in meningococcal strains.
  • To determine the prevalence of meningococcal strains with specific epitope alterations.

Main Methods:

  • Gene cloning and DNA sequencing of the porA gene.
  • Comparison of the sequenced gene with a reference strain.
  • Epitope analysis using monoclonal antibodies and synthetic peptides.
  • Assessment of complement-mediated bactericidal activity.

Main Results:

  • A point mutation in the porA gene was identified, leading to a single amino acid change in the P1.16 epitope.
  • Monoclonal antibodies specific for P1.16 did not react with peptides from the altered epitope.
  • The altered epitope (P1.16b) rendered the isolate resistant to complement-mediated bactericidal killing.
  • Infections caused by Neisseria meningitidis with the P1.16b epitope were widespread in England and Wales.

Conclusions:

  • The identified porA gene mutation is responsible for the altered P1.16 epitope in Neisseria meningitidis.
  • This epitope alteration affects immune recognition and host defense mechanisms.
  • The widespread distribution of strains with the P1.16b epitope highlights its epidemiological significance.

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