US Army Scientists Develop Novel Anthrax Treatment
By modifying an enzyme produced by the bacterium that causes anthrax, US Army scientists were able to protect mice from infection with the deadly disease.
Their findings, published in Science Translational Medicine, suggest a potential therapeutic strategy for treating multidrug-resistant strains of anthrax, and could aid in the development of new treatments for other bacterial infections.
Bacillus anthracis, the bacterium that causes anthrax, is one of the most significant bioterrorism threats, as well as a public health challenge in many places around the world. Its disease-causing capability arised from three main components – lethal toxin, oedema toxin, and the capsule. Researchers in this study developed a method to degrade the capsule surrounding the bacterium, allowing it to be ingested and destroyed by white blood cells, reducing virulence.
There is increasing concern about strains of anthrax that appear to be resistant to treatment with known antibiotics, said Arthur M. Friedlander, MD, the paper’s senior author. He and his team explored 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. 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 utilised recombinant DNA technology and protein engineering methods to engineer and reconfigure the enzyme in new ways.”
Those “engineering changes” included enhancing stability and making production easier, and pegylation, to improve pharmacokinetics. 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 out of 10 mice infected with anthrax spores from a nontoxigenic encapsulated strain were completely protected after treatment with PEG-CapD-CPS334C, compared to only 1 of 10 control mice surviving. Similarly, treatment of mice infected with a fully virulent encapsulated strain using PEG-CapD-CPS334C protected 8 of 10, while only 2 of 10 controls 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-catalysed 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 the treatment of soldiers exposed to anthrax through natural means or enemy attacks.
Source: EurekAlert!
