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Published on: November 5, 2019
Opa protein repertoires of disease-causing and carried meningococci
Martin J Callaghan1, Caroline Buckee, Noel D McCarthy
1Dept of Paediatrics, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Headington, Oxford OX3 9DU, United Kingdom. martin.callaghan@paediatrics.ox.ac.uk
Abstract:
The meningococcal Opa proteins play an important role in pathogenesis by mediating invasion of human cells. The aim of this investigation was to determine whether carried and disease-associated meningococci possess different Opa repertoires and whether the diversity of these proteins is associated with clinical severity of disease. Opa repertoires in 227 disease-associated meningococci, isolated in the United Kingdom over a period of 6 years, were compared to the repertoires in 190 asymptomatically carried meningococci isolated in the United Kingdom from a contemporary, nonepidemic period. Multidimensional scaling (MDS) was employed to investigate the association between Opa repertoires and multilocus sequence typing (MLST) genotypes. Associations with clinical severity were also analyzed statistically. High levels of diversity were observed in opa alleles, variable regions, and repertoires, and MDS revealed that MLST genotypes were strongly associated with particular Opa repertoires. Individual Opa proteins or repertoires were not associated with clinical severity, though there was a trend toward an association with the opaD locus. Meningococcal Opa repertoire is strongly linked to MLST genotype irrespective of epidemiological sampling and therefore correlates with invasiveness. It is not, however, strongly associated with severity of meningococcal disease.
Insights
Meningococcal Opa protein repertoires, crucial for cell invasion, strongly correlate with multilocus sequence typing (MLST) genotypes, indicating invasiveness. However, Opa diversity does not significantly link to the clinical severity of meningococcal disease.
Area of Science:
- Microbiology
- Pathogenesis
- Genetics
Background:
- Meningococcal Opa proteins are key virulence factors mediating Neisseria meningitidis invasion of human cells.
- Understanding Opa protein diversity is crucial for deciphering meningococcal pathogenesis and disease outcomes.
Purpose of the Study:
- To compare Opa protein repertoires between disease-associated and asymptomatically carried Neisseria meningitidis.
- To investigate the association between Opa repertoire diversity and the clinical severity of meningococcal disease.
Main Methods:
- Comparative analysis of Opa repertoires from 227 disease-associated and 190 carried meningococcal isolates.
- Multidimensional scaling (MDS) to correlate Opa repertoires with multilocus sequence typing (MLST) genotypes.
- Statistical analysis to assess the association between Opa diversity and clinical severity.
Main Results:
- High diversity observed in Opa alleles, variable regions, and repertoires.
- MDS revealed a strong association between MLST genotypes and specific Opa repertoires.
- No significant association found between individual Opa proteins or repertoires and clinical severity, though opaD locus showed a trend.
Conclusions:
- Meningococcal Opa repertoire is strongly linked to MLST genotype, irrespective of epidemiological context, correlating with invasiveness.
- Opa protein repertoire diversity is not a strong predictor of meningococcal disease severity.
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