Opacity-associated adhesin repertoire in hyperinvasive Neisseria meningitidis

Abstract

The opacity (Opa) proteins mediate a variety of interactions between the bacterium Neisseria meningitidis and its human host. These interactions are thought to be of central importance in both the asymptomatic colonization of the nasopharynx and the sporadic occurrence of meningococcal disease. The receptor specificities of a limited number of Opa protein variants have been explored, but the high level of amino acid sequence diversity among variants has complicated the assignment of specific roles to individual Opa variants or combinations of variants. In addition, the distribution of Opa protein variants among diverse meningococci, information that is potentially informative for studies of Opa function, is poorly understood. A systematic survey of the genetic diversity in the four opa gene loci in each of 77 meningococcal isolates was undertaken. These isolates were representative of the seven hyperinvasive meningococcal clonal complexes that caused the majority of meningococcal disease over the last 50 years. Consistent with previous studies, a high level of sequence diversity was observed among the opa genes and the proteins that they encoded; however, particular sets of Opa protein variants were consistently associated with each of the clonal complexes over time periods often spanning decades and during global spread. These observations were consistent with the postulate that particular combinations of Opa proteins confer fitness advantages to individual clonal complexes and have implications for studies of Opa function and the inclusion of Opa proteins in novel meningococcal vaccines.

FIG. 1.

Predicted secondary structural topology of Opa proteins. SV, semivariable region located in putative loop 1; HV1 and HV2, two hypervariable regions, located in putative loops 2 and 3, respectively. The regions of opa genes sequenced in this study are indicated.

FIG. 2.

Maximum likelihood phylogenies of concatenated MLST alleles (A), porA, porB, and fetA alleles (B), and opa sequences (C). Based on concatenated antigen allele sequences alone (phylogenies B and C), isolates clustered into genetically related groups, consistent with a phylogeny reconstructed from concatenated MLST alleles (phylogeny A).