Bacillus anthracis protease InhA regulates BslA-mediated adhesion in human endothelial cells

Area of Science:

• Microbiology
• Pathogenesis
• Bacterial Virulence Factors

Background:

• Bacillus anthracis disseminates within hosts by regulating endothelial cell attachment.
• BslA (Bacillus anthracis S-layer Protein A) is crucial for bacterial adhesion to human endothelial cells.
• The precise bacterial mechanisms controlling BslA-mediated adhesion are not fully understood.

Purpose of the Study:

• To investigate the role of InhA (immune inhibitor A), a B. anthracis protease, in regulating BslA levels and bacterial adhesion.
• To test the hypothesis that InhA influences BslA activity, thereby affecting B. anthracis binding to endothelium.

Main Methods:

• Utilized the Sterne 7702 strain of B. anthracis.
• Employed inhA mutant and complementation analyses in adhesion and invasion assays.
• Conducted Western blot and InhA inhibitor assays to assess protein levels and degradation.

Main Results:

• InhA was found to downregulate BslA activity, reducing B. anthracis adhesion and invasion in human brain endothelial cells.
• BslA protein levels were significantly higher in ΔinhA mutants compared to wild-type and complemented strains, indicating an inverse relationship between InhA and BslA expression.
• Purified InhA degraded BslA in a concentration- and time-dependent manner.

Conclusions:

• InhA protease plays a regulatory role in BslA-mediated vegetative cell adhesion and invasion by Bacillus anthracis.
• This study elucidates a key bacterial mechanism controlling bacterial-host cell interactions during anthrax infection.