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Pneumococcal capsule expression is controlled through a conserved, distal cis-regulatory element during infection
David G Glanville1, Ozcan Gazioglu2, Michela Marra1
1Department of Microbiology and Immunology, Loyola University Chicago, Maywood, Illinois, United States of America.
Plos Pathogens
|January 31, 2023
Summary
Control of Streptococcus pneumoniae capsule synthesis is critical for infection. Two transcription factors, SpxR and CpsR, regulate this via a cis-regulatory element (37-CE), with minor changes causing loss of virulence.
Area of Science:
- Microbiology
- Molecular Biology
- Pathogenesis
Background:
- Streptococcus pneumoniae causes significant global bacterial pneumonia.
- The pneumococcal capsule, a key virulence factor, varies between serotypes, influencing disease severity.
- Regulation of capsule synthesis is crucial for pneumococcal infection.
Purpose of the Study:
- To identify and characterize the regulatory mechanisms controlling pneumococcal capsule synthesis.
- To investigate the role of specific transcription factors and cis-regulatory elements in capsule production.
- To understand how variations in these regulatory elements contribute to serotype-specific disease outcomes.
Main Methods:
- In vivo and in vitro experimental approaches.
- Analysis of transcription factor interactions with cis-regulatory elements.
- Genetic manipulation of the 37-CE sequence to assess virulence.
- Structural analysis of SpxR interactions.
Main Results:
- Two conserved transcription factors, SpxR and CpsR, regulate capsule synthesis via a distal cis-regulatory element (37-CE).
- A three-nucleotide change in the 37-CE renders Streptococcus pneumoniae avirulent.
- SpxR forms a trimeric quaternary structure that interacts with the 37-CE to repress capsule synthesis in the airways.
- Variations in the 37-CE sequence exist across different pneumococcal serotypes.
Conclusions:
- The 37-CE acts as a critical molecular switch controlling pneumococcal capsule synthesis.
- SpxR-mediated regulation of the 37-CE is essential for pneumococcal virulence.
- The 37-CE represents a potential target for novel therapeutic strategies against pneumococcal infections.
- Serotype-specific variations in the 37-CE likely contribute to differential disease severity observed in Streptococcus pneumoniae infections.
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