Thursday, February 2, 2023
News on Pathogens and Preparedness
Global Biodefense
  • Featured
  • COVID-19
  • Funding
  • Directory
  • Jobs
  • Events
  • Subscribe
No Result
View All Result
  • Featured
  • COVID-19
  • Funding
  • Directory
  • Jobs
  • Events
  • Subscribe
No Result
View All Result
Global Biodefense
No Result
View All Result
Home Defense + Military

Stopping Lethal Anthrax Using an Enzyme to Disrupt the Bacterial Capsule

by Global Biodefense Staff
December 8, 2021
Stopping Lethal Anthrax Using an Enzyme to Disrupt the Bacterial Capsule

Capsule removal from Bacillus anthracis by treatment with Capsule Depolymerase (capsule shown in red). Credit: Photomicrograph by Wilson J. Ribot, USAMRIID

Scientists have demonstrated that modifying an enzyme produced by the bacterium that causes anthrax can protect mice from infection with the deadly disease. Their findings suggest a potential therapeutic strategy for treating multidrug-resistant strains of anthrax, and could lead to new treatments for other bacterial infections.

Bacillus anthracis, the bacterium that causes anthrax, is recognized as one of the most significant bioterrorism threats, as well as a public health challenge in many parts of the world. Three main components allow it to cause disease—lethal toxin, edema toxin, and capsule. In this study, the researchers developed a method to degrade the capsule surrounding the bacterium, allowing it to be ingested and destroyed by the white blood cells—thus reducing virulence.

Public health officials have become increasingly concerned about strains of anthrax that appear to be resistant to treatment with known antibiotics, according to Arthur M. Friedlander, M.D. He and his team at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) worked with investigators at the U.S. Naval Research Laboratories, the University of Washington in Seattle, and the University of California at Davis to explore alternative treatment approaches that do not rely on the use of antibiotic drugs.

One promising avenue is to make the bacterium more susceptible to the innate immune system—the human body’s first line of defense against a pathogenic “invader.” The innate immune response consists of physical, chemical and cellular defenses that work to immediately prevent the spread of foreign pathogens throughout the body. Enzymes known as capsular depolymerases, which are naturally produced by several classes of bacteria, have emerged as a potential new line of antivirulence agents.

“Identification of the capsule depolymerase enzyme within the anthrax bacillus led us to attempt to use that enzyme to remove the capsule,” said Friedlander. “When this proved successful, we utilized recombinant DNA technology and protein engineering methods to engineer and reconfigure the enzyme in new ways.”

 Those “engineering changes” included circular permutation by protein design, to enhance stability and make the enzyme easier to produce, and pegylation, which improves the enzyme’s pharmacokinetics—the properties that allow it to be absorbed and properly distributed within the body. The team then tested the pegylated enzyme, known as PEG-CapD-CPS334C, to be sure it had retained its enzymatic activity.

In the study, 10 of 10 mice infected with anthrax spores from a nontoxigenic encapsulated strain were completely protected after treatment with PEG-CapD-CPS334C, while only 1 of 10 mice receiving a control treatment survived. Similarly, treatment of mice infected with a fully virulent encapsulated strain using PEG-CapD-CPS334C protected 8 of 10 animals, while only 2 of 10 control animals survived.

“This strategy renders B. anthracis susceptible to the innate immune responses and does not rely on antibiotics,” the authors concluded. “These findings suggest that enzyme-catalyzed removal of the capsule may be a potential therapeutic strategy for the treatment of multidrug-resistant anthrax and other bacterial infections.”

It could also allow servicemembers exposed to anthrax through natural or other means to be treated at the time of exposure or shortly thereafter in forward areas where advanced diagnostics and treatments may not be readily available.

Treatment of Experimental Anthrax with Pegylated Circularly Permuted Capsule Depolymerase. Science Translational Medicine, 8 Dec 2021.

Tags: AnthraxDrug DevelopmentEditor PickSelect AgentsUSAMRIID

Related Posts

DARPA Selects Teams to Develop Vaccine Durability Prediction Model
Medical Countermeasures

DARPA Selects Teams to Develop Vaccine Durability Prediction Model

January 13, 2023
small glass vials on an assembly line await filling of vaccine solution
Industry News

Sabin Vaccine Institute to Advance Ebola Sudan and Marburg Vaccines with New BARDA Funding

January 12, 2023
How Are Bivalent COVID Vaccines Stacking Up Against Omicron?
Infectious Diseases

How Are Bivalent COVID Vaccines Stacking Up Against Omicron?

January 12, 2023
NISTCHO: New Living Reference Material for Producing Monoclonal Antibodies
Medical Countermeasures

NISTCHO: New Living Reference Material for Producing Monoclonal Antibodies

January 12, 2023
Load More

Latest News

Partner Therapeutics’ Novel Approach to Stratify Sepsis Patients Gains Backing From BARDA

Biopreparedness Research Virtual Environment (BRaVE) Initiative Backed by $105M DOE Funding

January 25, 2023
Influenza Proteins Tilt and Wave in ‘Breath-like’ Motions

Influenza Proteins Tilt and Wave in ‘Breath-like’ Motions

January 25, 2023
Biodefense Headlines – 24 January 2023

Biodefense Headlines – 24 January 2023

January 24, 2023
Biodefense Headlines – 17 January 2023

Biodefense Headlines – 17 January 2023

January 17, 2023

Subscribe

  • About
  • Contact
  • Privacy
  • Subscribe

© 2022 Stemar Media Group LLC

No Result
View All Result
  • Featured
  • COVID-19
  • Funding
  • Directory
  • Jobs
  • Events
  • Subscribe

© 2022 Stemar Media Group LLC