VirB, a key transcriptional regulator of Shigella virulence, requires a CTP ligand for its regulatory activities

Area of Science:

• Microbiology
• Molecular Biology
• Biochemistry

Background:

• Shigella causes bacillary dysentery, a major cause of diarrheal deaths globally.
• Virulence is regulated by the VirB protein, a transcriptional regulator.
• Identifying novel drug targets is crucial due to rising antibiotic resistance.

Approach:

• Investigated the VirB protein's molecular function and evolutionary relationship within the ParB superfamily.
• Determined VirB's ligand-binding properties using biochemical assays.
• Utilized site-directed mutagenesis to identify key residues involved in ligand binding and virulence.

Key Points:

• VirB belongs to a fast-evolving clade of the ParB superfamily, distinct from DNA partitioning functions.
• VirB specifically binds the nucleoside triphosphate, cytidine triphosphate (CTP).
• Mutations affecting CTP binding impair VirB's anti-silencing activity and virulence phenotypes.

Conclusions:

• This study reveals VirB as a bona fide CTP-binding protein.
• Establishes a direct link between VirB-CTP interactions and Shigella virulence.
• Expands the known functions of the ParB superfamily and identifies potential therapeutic avenues.