Genetic Diversity of the Pneumococcal Capsule: Implications for Molecular-based Serotyping

Mary Catherine McEllistrem


Future Microbiol. 2009;4(7):857-865. 

In This Article


The burden of invasive pneumococcal disease, while dramatically reduced in the PCV7 era, is still a significant cause of morbidity and mortality in the USA. In addition, serotype replacement with non-PCV7 serotypes is already causing an increase in invasive disease in some populations. Furthermore, the conjugate vaccines only provide modest protection against pneumonia and otitis. As a result, monitoring the seroepidemiology of pneumococcal disease in the conjugate vaccine era is of critical importance. On the surface, a reliable, cost-effective, objective and validated molecular- or immunology-based serotyping method seems feasible.

However, the plasticity of pneumococcus is a double-edged sword. The marked heterogeneity of the capsular genes is superbly suited for generating a capsular-based serotyping method. For example, PCR-based methods can readily detect strains from unrelated serotypes. However, SNPs alone can alter serotypes within a serogroup, and some unrelated serotypes have remarkably similar capsular operons. For these serotypes, sequencing is required. However, while sequencing key genes and RFLPs of capsular genes can potentially differentiate strains from related serotypes, some SNPs are not clinically important and result in a confusing and complicated serotyping classification scheme. Moreover, even these methods have not yet been able to accurately serotype strains from all 91 known serotypes. The multibead immunologic assay shows great promise; however, it is unclear when sufficient monoclonal antibodies will be available to serotype all known serotypes. Moreover, such an assay could be too costly, given the need for a large number of monoclonal antibodies and a laboratory capable of performing and analyzing flow cytometry. Thus, despite the inability of the quellung reaction to detect the new serotypes (6C and subtype 11A), this method remains the gold standard for monitoring the changing seroepidemiology trends in the conjugate vaccine era.


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