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Characterisation of the genetic mutation driving enhanced superantigen SpeA expression in Streptococcus pyogenes M1UK (second SP1448)

ABSTRACT: A new variant of group A Streptococcus (GAS) serotype M1 (designated ‘M1UK’) has been reported in the United Kingdom, linked with seasonal scarlet fever surges, marked increase in invasive infections, and exhibiting enhanced expression of the superantigen SpeA. The progenitor GAS ‘M1global’ and M1UK clones can be differentiated by 27 SNPs and 4 indels, yet the mechanism for speA upregulation is unknown. Here we investigate the previously unappreciated expansion of M1UK in Australia, now isolated from the majority of serious infections caused by serotype M1 GAS. M1UK sub-lineages circulating in Australia also contain a novel toxin repertoire associated with epidemic scarlet fever causing GAS in Asia. A single SNP in the M1UK tmRNA gene ssrA drives enhanced SpeA superantigen expression as a result of ssrA terminator readthrough in the M1UK lineage. This represents a new paradigm of toxin expression and urges enhanced international surveillance.

ORGANISM(S): Streptococcus pyogenes

PROVIDER: GSE212242 | GEO | 2023/01/30

REPOSITORIES: GEO

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Characterisation of the genetic mutation driving enhanced superantigen SpeA expression in Streptococcus pyogenes M1UK (second SP1380)

Project description:A new variant of group A Streptococcus (GAS) serotype M1 (designated ‘M1UK’) has been reported in the United Kingdom, linked with seasonal scarlet fever surges, marked increase in invasive infections, and exhibiting enhanced expression of the superantigen SpeA. The progenitor GAS ‘M1global’ and M1UK clones can be differentiated by 27 SNPs and 4 indels, yet the mechanism for speA upregulation is unknown. Here we investigate the previously unappreciated expansion of M1UK in Australia, now isolated from the majority of serious infections caused by serotype M1 GAS. M1UK sub-lineages circulating in Australia also contain a novel toxin repertoire associated with epidemic scarlet fever causing GAS in Asia. A single SNP in the M1UK tmRNA gene ssrA drives enhanced SpeA superantigen expression as a result of ssrA terminator readthrough in the M1UK lineage. This represents a new paradigm of toxin expression and urges enhanced international surveillance.

2023-01-30 | GSE212241 | GEO

Characterisation of the genetic mutation driving enhanced superantigen SpeA expression in Streptococcus pyogenes M1UK (second 5448)

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Characterisation of the genetic mutation driving enhanced superantigen SpeA expression in Streptococcus pyogenes M1UK (initial)

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Characterisation of a novel covS SNP identified in Australian Group A Streptococcus isolates derived from the M1UK lineage

Project description:Group A Streptococcus (GAS) is a human-adapted pathogen responsible for a variety of diseases. The GAS M1UK lineage has contributed significantly to the recently reported increases in scarlet fever and invasive infections, however the basis for its evolutionary success is not yet fully understood. During the transition to systemic disease, the M1 serotype is known to give rise to spontaneous mutations in the CovRS two-component transcriptional regulation system that confer a fitness advantage during invasive infections. Mutations that inactivate CovS function result in the de-repression of key GAS virulence factors such as Streptolysin O (SLO), a pore-forming toxin and major trigger of inflammasome/interleukin-1-dependent inflammation. Conversely, expression of the streptococcal cysteine protease SpeB, which is required during initial stages of colonisation and onset of invasive disease, is typically lost in such mutants. In this study, we identified and characterised a novel covS mutation detected in three separate invasive M1UK isolates. The resulting CovSAla318Val mutation caused a significant upregulation of SLO resulting in increased inflammasome activation in human THP-1 macrophages, indicating an enhanced inflammatory potential. Surprisingly, SpeB production was unaffected. Site-directed mutagenesis was performed to assess the impact of this mutation on virulence and global gene expression. We found that the CovSAla318Val mutation led to subtle, virulence-specific changes of the CovRS regulon compared to previously characterised covS mutations, highlighting an unappreciated level of complexity in CovRS-dependent gene regulation. Continued longitudinal surveillance is warranted to determine whether this novel covS mutation will expand in the M1UK lineage.

2024-10-28 | GSE280498 | GEO

Characterisation of the genetic mutation driving enhanced superantigen SpeA expression in Streptococcus pyogenes M1UK

Project description:Characterisation of the genetic mutation driving enhanced superantigen SpeA expression in Streptococcus pyogenes M1UK

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Characterisation of the genetic mutation driving enhanced superantigen SpeA expression in Streptococcus pyogenes M1UK (initial)

Project description:Characterisation of the genetic mutation driving enhanced superantigen SpeA expression in Streptococcus pyogenes M1UK (initial)

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Characterisation of the genetic mutation driving enhanced superantigen SpeA expression in Streptococcus pyogenes M1UK (second SP1380)

Project description:Characterisation of the genetic mutation driving enhanced superantigen SpeA expression in Streptococcus pyogenes M1UK (second SP1380)

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Characterisation of the genetic mutation driving enhanced superantigen SpeA expression in Streptococcus pyogenes M1UK (second SP1448)

Project description:Characterisation of the genetic mutation driving enhanced superantigen SpeA expression in Streptococcus pyogenes M1UK (second SP1448)

| PRJNA874703 | ENA

Characterisation of the genetic mutation driving enhanced superantigen SpeA expression in Streptococcus pyogenes M1UK (second 5448)

Project description:Characterisation of the genetic mutation driving enhanced superantigen SpeA expression in Streptococcus pyogenes M1UK (second 5448)

| PRJNA874702 | ENA

Microarray analysis of genes involved in Streptolysin S immunity

Project description:Group A Streptococcus (GAS) is one of the world’s most successful pathogens, causing a multitude of common infections such as pharyngitis, cellulitis, and impetigo. It is also responsible for more severe diseases such as rheumatic fever, necrotizing fasciitis, and toxic shock syndrome. Group A Streptococcus produces a powerful peptide toxin known as streptolysin S (SLS). Although recent advances have begun to uncover the structure of SLS, many questions remain as to its route of synthesis, export and function. A fundamental yet unanswered question about SLS is the mechanism employed by GAS to resist the effects of its own toxin. To address this question, we developed a unique microarray-based approach aimed at identifying bacterial genes involved in SLS immunity. We measured changes in gene expression in a non-SLS producing GAS strain (∆SLS) after exposure to active SLS, as well as to an inactive SLS isoform. Initial exposure of a non-SLS producing GAS to the native SLS toxin resulted in significant upregulation of several gene candidates. Proteins encoded by these gene candidates were produced and tested for their ability to neutralize SLS toxin activity in vitro. The protein encoded by the gene Spy_0787 decreased the cytolytic activity of wt SLS by 50%. Bacterial immunity is still a relatively unknown and unexplained phenomena. Insights into how toxin-producing microorganisms achieve resistance against the effects of their own toxin could uncover important therapeutic targets to neutralize virulence factors such as SLS, as well as other related peptide toxins. The microarray technique described here can be leveraged to other microbial systems to understand how microorganisms in general react to antibacterial and cytotoxic compounds for which the mechanism of action is unknown.

2013-09-01 | GSE48775 | GEO

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