drs (Distantly Related sic ) Gene Polymorphisms among emm12 -Type Streptococcus pyogenes Isolates

Abstract

Twenty-eight emm12-type Streptococcus pyogenes isolates from patients with invasive and noninvasive infections or from asymptomatic carriers were genetically typed. Sequencing of drs (distantly related sic [streptococcal inhibitor of complement]) genes identified two novel alleles and revealed a polymorphism for drs similar to that of sic. No association was observed between the five different drs alleles and the five restriction patterns of the vir regulon for the isolates studied. These data suggest that drs sequencing may be useful for further differentiation of S. pyogenes isolates with emm12 and identical vir regulon restriction patterns.The worldwide emergence of invasive Streptococcus pyogenes infections since the first description of streptococcal toxic shock syndrome almost 20 years ago (4) and the persistence of these infections are still unexplained (22). Particularly, isolates with prevalent emm types, largely emm1, followed by emm3, emm28, and emm12, have the ability to persist in the human environment for long periods, despite the fact that the world's population has likely been exposed to these strains on numerous occasions. Results of established molecular typing methods, including restriction fragment length polymorphism pattern analysis, random amplified polymorphic DNA (RAPD) analysis, and multilocus sequence typing, have revealed only very few individual clones of invasive emm1-type isolates over the past 2 decades (6, 17). Moreover, identical strains have also accounted for less serious infections, such as pharyngitis, cellulitis, and even asymptomatic carriage. Whether or not the high prevalence and persistence of such strains are due to an absence of protective immunity in a significant portion of the human population or to changes in the protective epitopes of the organism remains unclear (5, 7). Previous studies have shown that subtle differences, e.g., in the surface structure of the M1 protein, render some strains resistant to immune sera. Moreover, it has been postulated that natural selection on human mucosal surfaces for variants of the sic gene encoding the streptococcal inhibitor of complement (SIC) contributes to the emergence or reemergence of emm1-type S. pyogenes (13). Sequencing of the highly polymorphic sic genes of 1,132 of emm1-type S. pyogenes isolates derived from global sources has previously shown a high level of allelic diversity, with 220 distinct genes coding for 215 SIC protein variants. This polymorphism of sic has been applied to genetic subtyping of S. pyogenes isolates with emm1 and thus unambiguously differentiated isolates from temporally clustered invasive disease episodes (11). While the sic gene has previously been detected only within the vir(mga) regulon of all S. pyogenes strains harboring emm1 and outside the vir(mga) regulon of S. pyogenes strains with emm57 (1, 10), in a most recent study on S. pyogenes isolates from Japan, the presence of the sic gene was also reported with different frequencies for isolates harboring either emm2, emm4, emm12, emm28...

Molecular heterogeneity among north Indian isolates of Group A Streptococcus

“…In contrast few samples from our study showed same emm type for isolates showing different VTs. Similar results have also been reported by Brandt et al. (2003) where they categorized emm 12 strains into different VTs.…”

“…The restriction pattern of Vir regulon of Indian GAS isolates was found to be different from the pattern obtained from other countries indicating Vir types prevalent in this region to be different from those of Australian (Gardiner et al. 1995) and German Vir types (Brandt et al. 2003).…”

DRS Is Far Less Divergent than Streptococcal Inhibitor of Complement of Group A Streptococcus

“…DRS (for "distantly related to SIC") is known to exhibit sequence homology with SIC in the signal sequence and in a proline-rich region (2) and also to share some biological functions with SIC (8); therefore, it is considered to be an equally important virulence factor. For DRS, only a few alleles have been described thus far (4). Recently, information regarding heterogeneous emm type prevalence in India has been reported (6,12,13), but there are no data on the virulence status of GAS from this region.…”

Inhibition of antimicrobial peptides by group A streptococci: SIC and DRS

“…In particular, the Nterminal region of DRS lacks ten out of the 15 tryptophan residues present in that of M1 SIC. All strains of DRS isolated in Europe so far contain two copies of the N-terminal region [6], whereas the drs genes analysed from M12 and M55 strains isolated in Australia contain only one copy of the N-terminal SRR [5]. Both proteins are highly negatively charged, with a pI of 4.18 (SIC) and 4.47 (DRS).…”

“…Sequencing of the sic gene from numerous M1 GAS isolates has shown that long repeats 1 and 2 are the least variable areas of the protein in terms of amino acid sequence (reviewed in [10]), although several isolates have been shown to contain variable numbers of long repeat 2. DRS is also polymorphic [6] and approximately six variants have been reported, although far fewer M12 and M55 isolates have been investigated.…”