Streptococcus pyogenes evades adaptive immunity through specific IgG glycan hydrolysis

Area of Science:

• Immunology
• Microbiology
• Glycobiology

Background:

• Streptococcus pyogenes (Group A Streptococcus; GAS) causes a range of human infections.
• GAS secretes EndoS, an enzyme targeting IgG N-glycans, but its in vivo role is unknown.
• IgG glycosylation is crucial for antibody effector functions.

Purpose of the Study:

• To investigate the in vivo impact of GAS EndoS on host IgG glycosylation during infection.
• To assess the role of EndoS-mediated IgG modification in GAS virulence and immune evasion.

Main Methods:

• Targeted mass spectrometry to analyze IgG glycosylation in human infection samples.
• In vitro assays assessing phagocytic killing of GAS strains with and without EndoS.
• Murine model of invasive GAS infection to evaluate bacterial virulence.

Main Results:

• Significant IgG glycan hydrolysis by EndoS was observed both locally and systemically in human infections.
• GAS lacking EndoS showed reduced resistance to phagocytosis in vitro.
• EndoS-deficient GAS exhibited attenuated virulence in a mouse model of invasive infection.

Conclusions:

• This study provides the first evidence of bacterial EndoS hydrolyzing host IgG glycans in vivo during infection.
• EndoS-mediated IgG modification is a mechanism of immune evasion employed by Streptococcus pyogenes.
• Findings have implications for understanding severe GAS pathogenesis, treatment strategies, and vaccine development.