Treatment of experimental anthrax with pegylated circularly permuted capsule depolymerase

Area of Science:

• Microbiology
• Biochemistry
• Immunology

Background:

• Anthrax, caused by *Bacillus anthracis*, is a dangerous bioweapon agent.
• Multidrug-resistant strains necessitate alternative therapeutic strategies.
• The antiphagocytic capsule is a key virulence factor of *B. anthracis*.

Purpose of the Study:

• To evaluate the therapeutic efficacy of pegylated capsule depolymerase (PEG-CapD-CP) against *Bacillus anthracis* infection.
• To assess the impact of pegylation on the pharmacokinetic and therapeutic properties of capsule depolymerase.

Main Methods:

• Developed a pegylated variant of capsule depolymerase (PEG-CapD-CP^S334C).
• Treated mice infected with *B. anthracis* spores with PEG-CapD-CP^S334C.
• Administered treatment 24 hours post-exposure, every 8 hours for 2 days.

Main Results:

• Complete protection (10/10 mice) was observed in mice infected with a nontoxigenic strain when treated with PEG-CapD-CP^S334C.
• 80% survival rate (8/10 mice) was achieved in mice infected with a virulent toxigenic strain using PEG-CapD-CP^S334C.
• Control groups treated with bovine serum albumin showed significantly lower survival rates.

Conclusions:

• Pegylation significantly improves the therapeutic potential of capsule depolymerase for anthrax treatment.
• Enzyme-catalyzed capsule removal renders *B. anthracis* susceptible to innate immune responses.
• This strategy offers a promising alternative for treating multidrug- or vaccine-resistant anthrax and other bacterial infections.