Comparative analysis of Streptococcus
16S rRNA sequences had indicated that SDSE was more closely related to GBS than to GAS [67
]. In contrast, we found that SDSE, which belongs to Lancefield groups C and G [3
], is more closely related to GAS than to other sequenced streptococci based on genome wide and gene level comparisons
SDSE is known to cause diseases very similar to those caused by GAS, such as pharyngitis, cellulitis, infective arthritis, vertebral osteomyelitis, and STSS [10
]. This similarity may be due, at least in part, to their conservation of a large number of genes for virulence factors. Figure shows a summary of putative virulence factors and proposed virulence functions in SDSE. SDSE shares most of the virulence factor genes of GAS, including streptolysin O, streptokinase, FCT-like regions, NADase, and DRS. However, GGS_124 and probably almost all other SDSEs lack SpeB, superantigens except for SpeG, and hyaluronan synthesis via hasABC
]. As spegg4
, which has about 1% of the mitogenic activity of GAS-derived SpeG, is the only gene encoding a protein homologous to superantigens, and most SDSE isolates do not harbor superantigen-like genes other than spegg
], it is highly unlikely that superantigens play a significant role in the pathogenesis of SDSE infection in humans.
Figure 7 Putative virulence factors and posited virulence function of SDSE. Cell-surface proteins, extracellular secreted proteins, metal transporters, and the two-component regulator CsrR/CsrS, which affect the expression of approximately 10% of all genes in (more ...)
Particular M (or emm
) types of GAS have been associated with certain streptococcal diseases [63
]. We therefore analyzed the virulence in a mouse model of several SDSE strains bearing different emm
-types, but we were unable to find a significant correlation between emm
-type of SDSE and virulence. Further studies are needed to provide further insight into the linkage between emm
type of SDSE and infectivity in humans.
Streptococcal phages are considered critical in horizontal gene transfer, especially in the transport of virulence factors [28
], in Streptococci
. Three prophage elements in GGS_124 were found to be homologous to GAS prophages in both nucleotide and amino acid sequences. The positions of prophage insertion were also conserved between GGS_124 and previously sequenced GAS prophages, suggesting that SDSE and GAS share the same phage species, and that horizontal gene transfer between SDSE and GAS has occurred. However, GGS_124 does not contain prophages that encode genes for superantigens, Sla, or MF. These phage encoded genes were also missing from all strains previously analyzed by a GAS microarray [31
]. Sdn is an exception, since it was detected in 4 of these 58 SDSE strains [31
]. These results showed that SDSE may have some resistance to infection by GAS phages carrying genes encoding virulence factors.
Prokaryotes possess the CRISPR/Cas system, which mediates resistance to infection by foreign DNA, such as viruses [26
]. GGS_124 has a CRISPR/Cas system, designated CRISPR1/Cas, whereas the other SDSE isolates analyzed in this study had another CRISPR/Cas system, designated CRISPR2/Cas. We found that SDSE strains usually have a higher total number of spacers than GAS, suggesting that prophage infection of SDSE was restricted to some extent, resulting in a smaller number of virulence factors located in the prophage regions of SDSE. Similar restrictions were observed in SESZ when compared with SESE. For example, the SESE 4047 genome, which contains no CRISPR, contains genes encoding virulence factors in prophage regions. In contrast, SESZ MGCS10565 and H70, which contain 26 and 18 spacers, respectively, do not carry any prophages. Thus, the CRISPR system in streptococci sharing prophages may play a substantial role in the spread of virulence factors among species. Alternatively, these virulence factors may not benefit to SDSE during carriage or disease, such that the integration of these specific phages is not selected for.