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Biological properties of a Streptococcus pyogenes mutant generated by Tn916 insertion in mga
B M Kihlberg1, J Cooney, M G Caparon
1Department of Cell and Molecular Biology, Lund University, Sweden.
Abstract:
The mga regulon of Streptococcus pyogenes contains genes which contribute to the pathogenicity and virulence of this significant human pathogen. Transposon insertional inactivation of the regulatory mga gene in a S. pyogenes strain of the clinically important M1 serotype, blocked the expression of four genes located downstream of mga. These genes encode the M1 protein, the IgG-binding protein H, protein SIC which is an extracellular inhibitor of complement, and the C5a peptidase which interferes with granulocyte migration. The wild-type strain is resistant to phagocytosis and adheres to human skin tissue sections; properties that were lost in the transposon mutant. Moreover, the mutant was less virulent to mice but more cytolytic to human lymphocytes, the latter due to an increased activity of streptolysin S, whereas the production of streptolysin O, another toxin of S. pyogenes, was not affected. The mga mutation was complemented in trans with an intact mga gene which restored the phenotype of the wild-type strain.
Insights
The mga regulon controls virulence factors in Streptococcus pyogenes. Inactivating the mga gene reduced M1 protein and SIC expression, affecting bacterial pathogenicity and host interactions.
Area of Science:
- Microbiology
- Pathogen Biology
- Molecular Genetics
Background:
- * Streptococcus pyogenes is a significant human pathogen.
- * The mga regulon plays a crucial role in S. pyogenes pathogenicity and virulence.
- * Virulence factors include M1 protein, IgG-binding protein H, and complement inhibitor SIC.
Purpose of the Study:
- * To investigate the function of the mga regulon in S. pyogenes.
- * To determine the impact of mga gene inactivation on virulence factors and bacterial properties.
- * To analyze the role of mga in host-pathogen interactions.
Main Methods:
- * Transposon insertional inactivation of the mga gene in an M1 serotype S. pyogenes strain.
- * Analysis of gene expression downstream of mga (M1 protein, protein H, SIC, C5a peptidase).
- * Assessment of bacterial properties: phagocytosis resistance, adherence, mouse virulence, and lymphocyte cytolysis.
Main Results:
- * mga inactivation blocked expression of M1 protein, protein H, SIC, and C5a peptidase.
- * The mutant lost resistance to phagocytosis and adherence to human skin.
- * Mutant showed reduced mouse virulence but increased lymphocyte cytolysis due to enhanced streptolysin S activity.
- * Complementation restored the wild-type phenotype.
Conclusions:
- * The mga regulon is essential for the expression of key virulence factors in S. pyogenes M1 serotype.
- * mga regulates bacterial adherence, phagocytosis resistance, and virulence.
- * Streptolysin S activity is inversely regulated by mga, impacting cytolysis.