Engineering an Enzyme To Treat Anthrax Without Antibiotics



During the "Amerithrax" assaults of 2001, anthrax-causing spores were sent to news organizations and members of Congress, infecting at least 22 individuals and killing 5. Antibiotic-resistant strains of the bacteria are a growing cause of concern, therefore researchers are preparing to battle them. Now, according to a paper published in the journal ACS Infectious Diseases today (September 14, 2022), a team has made headway toward the development of a medication that might treat the infection in mice without the use of antibiotics.

A gram-positive, rod-shaped bacteria called Bacillus anthracis can cause anthrax infection when its spores are consumed, inhaled, or come into contact with a skin wound. Infection with anthrax can cause breathing problems, skin sores, or even death. Although there are medications that can combat anthrax, over time drug resistance can develop.

The B. anthracis bacteria's capsule can be broken apart by a designed enzyme with fragments of antibody attached, enabling the immune system to respond. Source: Reproduced with permission from ACS Infectious Diseases, DOI: 10.1021/acsinfecdis.2c00227

The ability of one strain of B. anthracis to encase itself in a poly-D-glutamic acid protective capsule makes this strain, known as the Ames strain, highly virulent. This helps the bacteria elude the human immune system by acting as an invisible cloak. The capsule substance is anchored to the bacteria by the B. anthracis enzyme CapD. However, earlier research has shown that the enzyme may be modified to break down the capsule rather than metabolize it, leaving the bacteria vulnerable to the immune system.

Additionally, studies have shown that giving mice the modified CapD can aid in the treatment of an Ames-strain anthrax infection without the need for medicines. Additionally, Patricia Legler and associates have shown that incorporating polyethylene glycol (PEG) into this variant of CapD can extend the enzyme's lifespan and boost mouse survival. The research team aimed to further improve the treatment in this latest trial.

The scientists combined the CapD protein with a piece of a mouse antibody to increase the lifetime of the re-engineered enzyme in the body and give it more punch. They also added PEG. Two CapD enzymes were consequently linked together, thereby increasing their ability to bind capsules. The study team developed various iterations of the enzyme and put them through numerous iterations of optimization, deleting and adding various parts, until they came up with a sequence that maintained its 3D shape and worked as expected over a range of pH levels.

This design exhibited decreased activity, but it persisted longer in a mouse model than the prior one without the fusion antibody. The discoveries represent a significant step toward a better treatment against antibiotic-resistant B. anthracis strains, according to the researchers, who note that additional study is required to create the perfect design.

The Defense Threat Reduction Agency provided funds, which the authors acknowledge.

By AMERICAN CHEMICAL SOCIETY 

Comments

Post a Comment

Popular posts from this blog

Do You Sleep on Your Back or Side? Here's The Research on 'Optimal' Sleep Positions

Image
William Dement, a renowned sleep researcher at Stanford University, is quoted as saying that after 50 years of study, the only reason he can think of for why we sleep is "because we become sleepy." Sleep certainly matters for our health and wellbeing even though it may be, as one researcher put it, "the sole major habit in quest of a function." Do we, however, have it right? What do studies on sleeping positions say? Is there a proper sleeping position? The majority of people favor sleeping on their side. This is encouraging news because people who sleep on their backs are more likely to have trouble falling asleep or breathing during the night. Most of the time, we have a tendency to shift around quite a bit at night. According to a study involving 664 sleepers, on average, participants slept on their side 54% of the time, their back 37% of the time, and their front 7% of the time. Males are more likely to change positions throughout the night and move their arms, ...
Read more

A Briefcase-Sized Box Is Already Making Oxygen on Mars

Image
Currently, the Martian atmosphere is in no way hospitable to Earthlings. It is formed primarily of carbon dioxide and is over 100 times less dense than Earth's atmosphere. It would soon stop breathing completely for any individuals who tried to breathe in it. A modest device, about the size of a suitcase, has been consistently extracting breathable oxygen from the Martian atmosphere on that sandy, arid, alien world. In order to manufacture breathing air for a human expedition to the red planet, it is the first demonstration of the processing of in situ resources for human use on another world. Its name is MOXIE (Mars Oxygen In-Situ Resource Utilization (ISRU) Experiment), and it is a device that utilizes electrolysis to separate Martian carbon dioxide into carbon monoxide and oxygen. It is mounted inside NASA's Perseverance rover. According to the researchers, MOXIE produced oxygen seven times as much between February 2021, when Perseverance arrived, until the end of 2021. Acco...
Read more

New DNA Research Unlocks Secrets of Native Rodents’ Rat Race to New Lands

Image
More than 150 different native rodent species from Australia, New Guinea, and Melanesian islands have had their DNA sequenced in recent studies. It provides a fuller understanding of their connections and the circumstances surrounding their expansion throughout the Pacific. The Australian National University's (ANU) Dr. Emily Roycroft, the study's lead author, said native rodents are an interesting but frequently underappreciated evolutionary group. Dr. Roycroft noted that over 150 species in Australia and New Guinea are unique to those regions and include the rakali, sometimes known as the "water rat," which is frequently spotted swimming in the lakes near Canberra. We now know relatively little about the history and development of native rodents, particularly those found in New Guinea. In order to obtain DNA from museum specimens up to 180 years old, including several extinct and secretive species, the study team developed a novel technique. "One Guadalcanal ra...
Read more