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Lateral genetic transfers between group A and G streptococci for M-like genes are ongoing
1Menzies School of Health Research, Darwin, Australia.
Abstract:
Previously we described a long-polymerase chain reaction (PCR) method to amplify a 4-7 kb target containing most of the components of the vir regulon (mga, emm-like genes and scpA) in a number of group A streptococcus (GAS) isolates. In contrast to GAS, strains of human group G streptococcus (GGS) gave approximately 1.6 or 1.8 kb products. Sequence analysis of the amplified products issued from GGS templates revealed a mosaic consisting of upstream sequence from mga (the gene for positive regulator of vir regulon), an unidentified open reading frame, a short segment of emm (the gene for M protein, an antiphagocytic molecule) and an upstream sequence of scp (C5a-peptidase gene). A full length scpG is present immediately downstream from the mosaic segment in the human GGS genome. The GGS PCR fragment did not code for mga or full length emm. All human GGS isolates are known to code for emm but the gene is separated from scpG by at least 10 kb. Our data, obtained using long-PCR and unrelated strains of GGS, confirm this. We could not detect a homologue of mga in human GGS by hybridization analysis. The mosaic sequence suggests that enbloc transfer of the vir regulon from GAS to a GGS progenitor may have occurred, following which deletion and rearrangement events may have taken place. Partial nucleotide sequences of emm corresponding to the variable domain of M proteins from three local GGS isolates were determined. One sequence (emmGGS6) is 99% identical to emm from a geographically separated isolate of GGS recently described.3 emmGGS6 also has significant homology with emm from a GAS strain (STDONALD) isolated from the same geographical area as was GGS6. The two emm sequences (emmGGS6 and emmSTDONALD) revealed frameshift-compensatory frameshift mutations relative to each other, contributing to lower amino acid homology between the two predicted M proteins. Since emmSTDONALD has no known relatives within the 80 or so emm sequences in the database, we speculate that it could have been laterally acquired from GGS. Horizontal transfers between GGS and GAS may be ongoing.
Insights
Group G Streptococcus (GGS) possess a unique mosaic gene sequence, suggesting horizontal gene transfer from Group A Streptococcus (GAS). This finding sheds light on the evolution of virulence factors in streptococcal pathogens.
Area of Science:
- Microbiology
- Genetics
- Molecular Biology
Background:
- Group A Streptococcus (GAS) possesses the vir regulon, including mga, emm, and scpA genes, crucial for virulence.
- Previous studies established a long-polymerase chain reaction (PCR) method for amplifying the GAS vir regulon components.
- Human Group G Streptococcus (GGS) isolates typically have the emm gene separated from the scpG gene.
Purpose of the Study:
- To investigate the genetic organization of the vir regulon components in human Group G Streptococcus (GGS) isolates.
- To compare the genetic makeup of GGS with that of Group A Streptococcus (GAS) regarding virulence genes.
- To explore potential horizontal gene transfer events between GAS and GGS.
Main Methods:
- Long-polymerase chain reaction (PCR) was employed to amplify genetic fragments from GGS isolates.
- Sequence analysis was performed on the amplified products to identify gene components and their arrangement.
- Hybridization analysis was used to detect homologous sequences, specifically for the mga gene in GGS.
- Partial nucleotide sequencing of emm genes from GGS isolates was conducted.
Main Results:
- GGS isolates yielded smaller PCR products (1.6-1.8 kb) compared to GAS (4-7 kb).
- The GGS amplified fragment contained a mosaic sequence including parts of mga, an unidentified ORF, a short emm segment, and scp gene sequences.
- Full-length mga and emm genes were not detected within the amplified GGS fragment, and mga homologues were absent in GGS.
- The emm gene in GGS is located at least 10 kb away from scpG, confirming previous findings.
- One GGS emm sequence (emmGGS6) showed high identity to another GGS isolate and significant homology to a GAS emm sequence (STDONALD).
- emmGGS6 and emmSTDONALD sequences exhibited frameshift mutations, resulting in lower amino acid homology.
Conclusions:
- The mosaic structure in GGS suggests a possible en bloc transfer of the vir regulon from GAS, followed by deletion and rearrangement.
- The emm gene in GGS appears to be acquired laterally, potentially from GAS, as indicated by sequence homology and mutations.
- Ongoing horizontal gene transfer between GGS and GAS is a plausible mechanism driving the evolution of virulence in these streptococcal species.