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Updated: Jul 24, 2025

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A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
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Interplay between human STING genotype and bacterial NADase activity regulates inter-individual disease variability.
Elin Movert1, Jaume Salgado Bolarin1, Christine Valfridsson1
1Department of Biology, Lund University, Sölvegatan 35, 223 62, Lund, Sweden.
Nature Communications
|July 6, 2023
Summary
Host STING genotype and Streptococcus pyogenes NADase activity determine invasive infection outcomes. Reduced STING binding plus high bacterial NADase activity leads to severe disease, while robust STING response offers protection.
Area of Science:
- Microbiology
- Immunology
- Genetics
Background:
- Invasive Streptococcus pyogenes infections exhibit variable severity due to host-pathogen genetic interactions.
- The STING pathway and type I Interferon (IFN) response are crucial in innate immunity against bacterial pathogens.
Purpose of the Study:
- To investigate the interplay between human STING genotype and bacterial NADase activity in regulating invasive Streptococcus pyogenes infection outcomes.
- To elucidate the mechanism by which bacterial NADase influences the host immune response.
Main Methods:
- Analysis of Streptococcus pyogenes-derived cyclic di-AMP (c-di-AMP) diffusion through streptolysin O pores.
- Assessment of STING activation and type I IFN production in macrophages.
- Genotyping of STING in patients with necrotizing S. pyogenes infections.
- Correlation of bacterial NADase activity with patient outcomes.
Main Results:
- Bacterial c-di-AMP activates STING and type I IFN response via streptolysin O pores.
- Bacterial NADase activity suppresses STING-mediated type I IFN production.
- A specific STING genotype with reduced c-di-AMP binding capacity, coupled with high bacterial NADase activity, correlates with poor patient outcomes in necrotizing infections.
Conclusions:
- Bacterial NADase possesses an immune-regulatory function, suppressing host type I IFN responses.
- The interaction between host STING genotype and bacterial NADase activity is a key determinant of invasive Streptococcus pyogenes infection severity and interindividual variability.
- Understanding this host-pathogen genotype interplay offers insights into disease pathogenesis and potential therapeutic targets.
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