Multilocus sequence typing of Streptococcus pyogenes representing most known emm types and distinctions among subpopulation genetic structures

Abstract

A long-term goal is to characterize the full range of genetic diversity within Streptococcus pyogenes as it exists in the world today. Since the emm locus is subject to strong diversifying selection, emm type was used as a guide for identifying a genetically diverse set of strains. This report contains a description of multilocus sequence typing based on seven housekeeping loci for 495 isolates representing 158 emm types, yielding 238 unique combinations of sequence type and emm type. A genotypic marker for tissue site preference (emm pattern) revealed that only 17% of the emm types displayed the marker representing strong preference for infection at the throat and that 39% of emm types had the marker for skin tropism, whereas 41% of emm types harbored the marker for no obvious tissue site preference. As a group, the emm types bearing the emm pattern marker indicative of no obvious tissue site preference were far less likely to have two distinct emm types associated with the same sequence type than either of the two subpopulations having markers for strong tissue tropisms (P < 0.002). In addition, all genetic diversification events clearly ascribed to a recombinational mechanism involved strains of only two of the emm pattern-defined subpopulations, those representing skin specialists and generalists. The findings suggest that the population genetic structure differs for the tissue-defined subpopulations of S. pyogenes. The observed differences may partly reflect differential host immune selection pressures.

FIG. 1.

Population snapshot by eBURST. The entire S. pyogenes database of 495 isolates is displayed as a single eBURST diagram, by setting the group definition to zero of seven shared alleles, which places all isolates in a single group. Each dot represents an ST, and the size of the dot reflects the number of GAS isolates in each ST for the set of 495 isolates under study. STs that differ by a single locus are linked with a solid line; clusters of linked isolates correspond to clonal complexes. Founder STs are labeled (arrows), although, except for ST65, the bootstrap support for the founders was low. The distribution and spacing of unlinked STs and clonal complexes in a population snapshot are not relational and provide no information about the genetic distances between them.