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Published on: February 19, 2019
The Cell Wall Deacetylases Spy1094 and Spy1370 Contribute to Streptococcus pyogenes Virulence
Tiger Aspell1, Adrina Hema J Khemlani1, Catherine Jia-Yun Tsai1,2
1Department of Molecular Medicine & Pathology, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
Abstract:
Streptococcus pyogenes, or Group A Streptococcus (GAS), is a strictly human pathogen that causes a wide range of diseases, including skin and soft tissue infections, toxic shock syndrome and acute rheumatic fever. We have recently reported that Spy1094 and Spy1370 of S. pyogenes serotype M1 are N-acetylglucosamine (GlcNAc) deacetylases. We have generated spy1094 and spy1370 gene deletion mutants in S. pyogenes and gain-of-function mutants in Lactococcus lactis. Similar to other cell wall deacetylases, our results show that Spy1094 and Spy1370 confer lysozyme-resistance. Furthermore, deletion of the genes decreased S. pyogenes virulence in a human whole blood killing assay and a Galleria mellonella (Greater wax moth) larvae infection model. Expression of the two genes in L. lactis resulted in increased lysozyme resistance and survival in whole human blood, and reduced survival of infected G. mellonella larvae. Deletion of the spy1370, but not the spy1094 gene, decreased resistance to the cationic antimicrobial peptide cecropin B, whereas both enzymes increased biofilm formation, probably resulting from the increase in positive charges due to deacetylation of the cell wall. In conclusion, Spy1094 and Spy1370 are important S. pyogenes virulence factors and might represent attractive targets for the development of antibacterial agents.
Insights
Streptococcus pyogenes enzymes Spy1094 and Spy1370 are key virulence factors. Deleting these genes reduces bacterial infection severity and increases susceptibility to antimicrobial peptides, suggesting they are potential antibacterial targets.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- Streptococcus pyogenes (Group A Streptococcus) causes numerous human diseases.
- Spy1094 and Spy1370 are N-acetylglucosamine (GlcNAc) deacetylases in S. pyogenes serotype M1.
- Cell wall deacetylases are known to confer resistance to lysozyme.
Purpose of the Study:
- To investigate the role of Spy1094 and Spy1370 in S. pyogenes virulence.
- To determine the impact of these enzymes on bacterial resistance mechanisms.
- To explore their potential as targets for novel antibacterial agents.
Main Methods:
- Generated gene deletion mutants of spy1094 and spy1370 in S. pyogenes.
- Created gain-of-function mutants in Lactococcus lactis.
- Assessed lysozyme resistance, human whole blood killing assays, Galleria mellonella infection models, and cecropin B resistance.
Main Results:
- Spy1094 and Spy1370 confer lysozyme resistance.
- Gene deletions decreased S. pyogenes virulence in vivo and in vitro.
- Expression in L. lactis enhanced resistance and virulence.
- Spy1370 deletion reduced cecropin B resistance; both increased biofilm formation.
Conclusions:
- Spy1094 and Spy1370 are significant virulence factors for S. pyogenes.
- These enzymes contribute to bacterial resistance and biofilm formation.
- They represent promising targets for developing new antibacterial therapies.
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