Anthrax SET Protein

Toxins play a major role in the pathogenesis of Bacillus anthracis by subverting the host defenses. However, besides toxins, B. anthracis expresses effector proteins, whose role in pathogenesis are yet to be investigated. Here we present that suppressor-of-variegation, enhancer-of-zeste, trithorax protein from B. anthracis ( Ba SET) methylates human histone H1, resulting in repression of NF-κB functions. Notably, Ba SET is secreted and undergoes nuclear translocation to enhance H1 methylation in B. anthracis -infected macrophages. Compared with wild type Sterne, delayed growth kinetics and altered septum formation were observed in the Ba SET knock-out ( Ba ΔSET) bacilli. Uncontrolled Ba SET expression during complementation of the BaSET gene in Ba ΔSET partially restored growth during stationary phase but resulted in substantially shorter bacilli throughout the growth cycle. Importantly, in contrast to Sterne, the Ba ΔSET B. anthracis is avirulent in a lethal murine bacteremia model of infection. Collectively, Ba SET is required for repression of host transcription as well as proper B. anthracis growth, making it a potentially unique virulence determinant. Background: The role of SET protein ( Ba SET) in B. anthracis life cycle was unknown until now. Results: Ba SET regulates NF-κB activation, septation, and infectivity. Conclusion: Ba SET is one of the key effectors for B. anthracis pathogenesis. Significance: Previous studies predict that SET protein may not have any role in lower organisms. Hence, this is the first report demonstrating SET protein function in a human pathogen.