Engineering an enzyme against antibiotic-resistant anthrax
This engineered enzyme with bits of antibody stuck to it can break apart the capsule of B. anthracis bacteria, allowing the immune system to fight back. Credit: Adapted from ACS Infectious Diseases, DOI: 10.1021/acsinfecdis.2c00227

At least 22 people were killed and five were injured in the 2001 "Amerithrax" attacks. Researchers are getting ready to fight back against antibiotic-resistant strains of thebacteria. A therapeutic that can treat the infection in mice without antibiotics is being developed by a team of researchers.

A cut in the skin is one of the ways that Bacillus anthracis can cause an illness. Difficult breathing, skin ulcers or even death can be caused by the infections. Resistance to antibiotics can happen over time.

The Ames strain of B. anthracis can hide in a protective capsule of poly-D-glutamic acid, which helps it evade the human immune system. The capsule material is anchored by a B. anthracis enzyme called CapD, but previous studies have shown that it can be degraded by the immune system. Studies have shown that the engineered CapD can be used to treat an Ames-strain anthrax without antibiotics. AddingPEG to this version of CapD can increase the lifespan of the mouse. The team wanted to make the treatment better.

To deliver a bigger punch and improve the re-engineering's lifetime in the body, the researchers fused the CapD protein with part of a mouse antibody. The two CapDidases bound together would double their capsule-binding power. The researchers created several versions of the enzyme and subjected them to a number of rounds of deletion and modification until they achieved a sequence that both held its 3D shape and performed as expected. The previous version of this construct had reduced activity but it lasted longer in the mouse model. The results of the research are an important step towards a better treatment against antibiotic-resistant B. anthracis strains.

More information: Engineering an Fc-fusion of a Capsule Degrading Enzyme for Treatment of Anthrax, ACS Infectious Diseases (2022). DOI: 10.1021/acsinfecdis.2c00227 Journal information: ACS Infectious Diseases