Whole-Genome Sequencing Reveals the Genetic Divergence of the emm1-2 Genotype Prevalent in India from the Globally Prevalent emm1, Supporting Its Classification as a Distinct Genotype ^†

The significant genetic diversity among Group A Streptococcal (GAS) strains isolated from various geographical regions presents serious challenges for treatment and vaccine development strategies. Our findings indicate that while the emm1 genotype is globally prevalent, it is rare in India. Instead, the emm1-2 genotype is more common. Our previous PCR- and microarray-based studies revealed both genetic similarities and differences between emm1-2 and emm1 strains based on limited data. Therefore, this study conducted a more comprehensive comparison of emm1-2 and emm1 strains at the whole-genome level.

We performed Multi-locus Sequence Typing (MLST) followed by whole-genome sequencing. Bioinformatic tools were employed to analyze genome sequences, phylogenetic relationships, and antibiotic resistance profiles.

The majority of emm1-2 strains belonged to MLST sequence types 530 and 1269, distinct from the emm1 strain (ST28). Meanwhile, the individual allelic profiles of at least five of the seven genes overlapped between emm1 and emm1-2, unlike other emm types. The overall genome size of emm1-2 was comparable to that of emm1 strains. However, whole-genome sequence-based phylogenetic analysis of multiple emm types revealed that emm1-2 strains formed a separate clade from emm1 strains. Additionally, emm1-2 strains were resistant to two additional classes of antibiotics compared to emm1 strains.

Although the similarity of emm1-2 to emm1 should be considered when evaluating its virulence, the genetic divergence of emm1-2, as shown by phylogenetic analysis based on whole-genome sequencing, supports its classification as a distinct emm type. This finding is important for both treatment and multivalent vaccine research.