The dual M protein systems have diverse biological characteristics, but both contribute to M18-type Group A
Xiaorui Zhou1, Haoshuai Song1, Fei Pan1
1MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Ministry of Agriculture Key Laboratory of Animal Bacteriology, Nanjing 210095, China.
Abstract:
M protein is a key surface virulence factor in Group A Streptococcus (GAS), Group C Streptococcus (GCS), and other streptococcal species. GAS encodes M protein using the emm gene, while GCS employs the szm (or sem) gene. In M18-type GAS, dual M protein systems exist, comprising both GAS and GCS M proteins (encoded separately by emm18 and spa18). The spa18 gene in M18-type GAS shares a conserved region highly similar to GCS's szm gene. Our study reveals that spa18 exhibits higher transcription levels than emm18 in M18-type GAS strains. The dual M protein systems defective mutant (Δemm18Δspa18) displays a smooth surface, whereas wild-type and single M protein gene mutants remain rough. M18 and SPA18 proteins possess distinct characteristics, showing varied binding properties and cytotoxicity effects on macrophages (THP-1) and keratinocytes (HaCaT). Both emm18 and spa18 genes contribute to the skin pathogenicity of M18-type GAS. Transcriptome analysis suggests the potential involvement of the mga gene in spa18 transcription regulation, while SpyM18_2047 appears to be specific to spa18 regulation. In summary, this research offers a crucial understanding of the biological characteristics of dual M protein systems in M18-type GAS, highlighting their contributions to virulence and transcriptional regulation.
Insights
Group A Streptococcus (GAS) M18 strains utilize dual M protein systems. These systems, involving both GAS and GCS M proteins, are crucial for virulence and skin pathogenicity in these bacteria.
Area of Science:
- Microbiology
- Molecular Biology
- Bacterial Pathogenesis
Background:
- M protein is a critical surface virulence factor in Group A Streptococcus (GAS) and Group C Streptococcus (GCS).
- M18-type GAS strains possess a unique dual M protein system, utilizing both GAS (emm18) and GCS (spa18) M proteins.
- The spa18 gene in M18-type GAS is homologous to the GCS szm gene.
Purpose of the Study:
- To investigate the biological characteristics and virulence contributions of the dual M protein systems in M18-type GAS.
- To analyze the transcriptional regulation of the emm18 and spa18 genes.
- To understand the distinct roles of M18 and SPA18 proteins in bacterial surface structure and host cell interactions.
Main Methods:
- Comparative gene analysis of emm18 and spa18.
- Construction and characterization of M18-type GAS mutants (Δemm18Δspa18).
- Assessment of bacterial surface morphology using electron microscopy.
- Evaluation of M18 and SPA18 protein binding properties and cytotoxicity.
- Transcriptome analysis to identify regulatory factors.
Main Results:
- spa18 shows higher transcription levels than emm18 in M18-type GAS.
- A mutant lacking both M protein genes (Δemm18Δspa18) exhibits a smooth surface, unlike the rough surface of wild-type and single-mutant strains.
- M18 and SPA18 proteins display distinct binding characteristics and differential cytotoxicity towards macrophages and keratinocytes.
- Both emm18 and spa18 genes are essential for the skin pathogenicity of M18-type GAS.
- The mga gene may regulate spa18 transcription, with SpyM18_2047 potentially playing a specific regulatory role.
Conclusions:
- The dual M protein system in M18-type GAS significantly contributes to bacterial virulence and surface characteristics.
- spa18 is a highly transcribed gene in this system and plays a vital role in pathogenicity.
- Distinct functional properties of M18 and SPA18 proteins mediate interactions with host cells.
- Transcriptional regulation of spa18 involves factors like mga and SpyM18_2047, offering insights into virulence factor control.
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