Enzyme engineering to treat anthrax without antibiotics

Researchers have taken a step toward developing a treatment that can treat antibiotic-resistant strains of anthrax in mice without antibiotics.

The spores that cause anthrax were mailed to news organizations and members of Congress during the 2001 “Amerithrax” attacks, sickening at least 22 people and killing five. Researchers are preparing to combat antibiotic-resistant types of bacteria, which are a growing concern. Now, the team has made progress toward creating a treatment that might treat infections in mice without the use of antibiotics, as reported today (September 14, 2022) in the journal. ACS Infectious Diseases.

Bacillus anthracis It is a gram-positive, rod-shaped bacterium that can lead to[{” attribute=””>anthrax infection through exposure to its spores, either by ingestion, inhalation, or a cut in the skin. Anthrax infection can lead to difficulty breathing, skin ulcers, or even death. Although antibiotics against anthrax exist, resistance to these drugs can occur over time.

Engineered 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

One type of B. anthracis, called the Ames strain, is particularly virulent because the bacteria can wrap itself in a protective capsule of poly-D-glutamic

To improve the re-engineered enzyme’s lifetime in the body and deliver a bigger punch, the scientists added PEG and fused the CapD protein with part of a mouse antibody. This resulted in two CapD enzymes bound together, which would essentially double its capsule-binding power. The research team created several versions of the enzyme and subjected them to many rounds of optimization, deleting and inserting different segments until they achieved a sequence that both held its 3D shape and performed as expected in a range of pH values.

When tested in a mouse model, this construct lasted longer than the previous version without the fused antibody, though it had reduced activity. The scientists say that more research is needed to produce the ideal construct, but the results are an important step toward a better treatment against antibiotic-resistant B. anthracis strains.

Reference: “Engineering an Fc-fusion of a Capsule Degrading Enzyme for Treatment of Anthrax” 14 September 2022, ACS Infectious Diseases.
DOI: 10.1021/acsinfecdis.2c00227

The authors acknowledge funding from the Defense Threat Reduction Agency.