High diversity within and low but significant genetic differentiation among geographic and temporal populations of the global Streptococcus pneumoniae.

Streptococcus pneumoniae is the major cause of invasive pneumococcal disease (IPD). However, the global population structure remains largely unexplored. In this study, we investigated the spatial and temporal patterns of genetic variation of S. pneumoniae based on archived multilocus sequence typing data from PubMLST.org. Our analyses demonstrated both shared and unique distributions of sequence types (STs) and allele types among regional populations. Among the 17,915 global STs, 36 representing 15,263 isolates were broadly shared among all six continents, consistent with recent clonal dispersal and expansion of this pathogen. The analysis of molecular variance revealed that >96% genetic variations were found within individual regional populations. However, though low (<4%), statistically significant genetic differentiation among regional populations were observed. Comparisons between non-clone-corrected and clone-corrected datasets showed that localized clonal expansion contributed significantly to the observed genetic differentiations among regions. Temporal analyses of the isolates showed that implementation of pneumococcal conjugate vaccine impacted the distributions of STs but the effect on population structure were relatively limited. Linkage disequilibrium analyses identified evidence for recombination in all continental populations, however, the inferred recombination was not random. We discussed the limitations and implications of our analyses to the global epidemiology and vaccine developments for S. pneumoniae.