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Updated: Sep 7, 2025

Visualization of Streptococcus pneumoniae within Cardiac Microlesions and Subsequent Cardiac Remodeling
Published on: April 7, 2015
Encapsulation of the septal cell wall protects Streptococcus pneumoniae from its major peptidoglycan hydrolase and
Joana Figueiredo1,2,3, Mafalda Xavier Henriques2, Maria João Catalão2,4
1Laboratory of Bacterial Cell Surfaces and Pathogenesis, UCIBIO-Applied Molecular Biosciences Unit, Department of Life Sciences, NOVA School of Science and Technology, Universidade Nova de Lisboa, Monte da Caparica, Portugal.
Abstract:
Synthesis of the capsular polysaccharide, a major virulence factor for many pathogenic bacteria, is required for bacterial survival within the infected host. In Streptococcus pneumoniae, Wze, an autophosphorylating tyrosine kinase, and Wzd, a membrane protein required for Wze autophosphorylation, co-localize at the division septum and guarantee the presence of capsule at this subcellular location. To determine how bacteria regulate capsule synthesis, we studied pneumococcal proteins that interact with Wzd and Wze using bacterial two hybrid assays and fluorescence microscopy. We found that Wzd interacts with Wzg, the putative ligase that attaches capsule to the bacterial cell wall, and recruits it to the septal area. This interaction required residue V56 of Wzd and both the transmembrane regions and DNA-PPF domain of Wzg. When compared to the wild type, Wzd null pneumococci lack capsule at midcell, bind the peptidoglycan hydrolase LytA better and are more susceptible to LytA-induced lysis, and are less virulent in a zebrafish embryo infection model. In this manuscript, we propose that the Wzd/Wze pair guarantees full encapsulation of pneumococcal bacteria by recruiting Wzg to the division septum, ensuring that capsule attachment is coordinated with peptidoglycan synthesis. Impairing the encapsulation process, at localized subcellular sites, may facilitate elimination of bacteria by strategies that target the pneumococcal peptidoglycan.
Insights
Streptococcus pneumoniae uses Wzd and Wze proteins to recruit the Wzg ligase to the cell division septum, ensuring capsule synthesis and bacterial virulence. This coordinated process is crucial for bacterial survival and can be targeted for therapeutic strategies.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- Capsular polysaccharide synthesis is vital for bacterial virulence and survival.
- In Streptococcus pneumoniae, Wze (tyrosine kinase) and Wzd (membrane protein) localize to the division septum, ensuring capsule presence.
- Regulation of capsule synthesis is critical for understanding bacterial pathogenesis.
Purpose of the Study:
- To investigate the interactions of Wzd and Wze with other proteins involved in pneumococcal capsule synthesis.
- To elucidate the mechanism by which capsule synthesis is regulated at the subcellular level.
- To identify potential targets for therapeutic strategies against Streptococcus pneumoniae.
Main Methods:
- Bacterial two-hybrid assays were employed to identify protein-protein interactions.
- Fluorescence microscopy was used to visualize protein localization within bacterial cells.
- Virulence was assessed using a zebrafish embryo infection model.
Main Results:
- Wzd was found to interact with Wzg, a putative capsule ligase, and recruit it to the division septum.
- This interaction was dependent on specific residues and domains of Wzd and Wzg.
- Wzd null mutants exhibited reduced capsule at midcell, increased susceptibility to lysis, and decreased virulence.
Conclusions:
- The Wzd/Wze protein pair is essential for recruiting Wzg to the division septum, ensuring coordinated capsule attachment and synthesis.
- This localized regulation of capsule synthesis is critical for Streptococcus pneumoniae virulence.
- Targeting the pneumococcal encapsulation process may offer novel therapeutic strategies.
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