Evidence of recombination and an antigenically diverse immunoglobulin A1 protease among strains of Streptococcus pneumoniae.

The genetic relationships among 114 isolates of Streptococcus pneumoniae representing mainly nine serotypes that frequently cause severe childhood disease in Northern Europe were examined by use of multilocus enzyme electrophoresis. A comparison was made of the corresponding antigenic variations of excreted immunoglobulin A1 (IgA1) proteases detected by enzyme neutralization assays. Allelic variation at 13 gene loci among 70 electrophoretic types disclosed a comparatively low mean genetic diversity per locus (H = 0.319). In contrast, IgA1 proteases showed extensive antigenic diversity as 17 different inhibition types were distinguished. A lack of overall clonality was apparent from the linkage equilibrium of alleles harbored by 28 isolates chosen to represent the genetic diversity of the study population. However, certain clones, such as those marked by identical electrophoretic type, serotype, and IgA1 protease type, persisted for a sufficiently long time to enable clonal spread between distant geographic areas. Among clonally related isolates, examples illustrating a shift of capsular serotype or IgA1 protease type supported the view that recombination occurs in vivo in corresponding genes. In conclusion, over time, horizontal genetic exchange appears to be sufficiently frequent to disrupt the clonal structure otherwise generated by binary fission in natural populations of S. pneumoniae. The clonal instability combined with considerable antigenic heterogeneity renders the pneumococcal IgA1 protease less attractive as a potential component of future vaccines.