US military medical institutions work together to counter bioweapon threats

Researchers from the Defense Threat Reduction Agency (DTRA), the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) and the Walter Reed Army Institute of Research are working together to develop a treatment to combat the threat of tularemia bacteria as a biological weapon . .

The bacterium that causes tularemia, Francisella tularensisdesignated a Tier 1 selected agent, “presenting the greatest risk of intentional abuse with the most significant potential for mass casualties,” designating it as a potential biological weapon, according to a Jan. 6, 2024, announcement by DTRA’s Chemical and Biological Technologies Division.

The initiative between DTRA, USAMRIID and the Walter Reed Army Institute of Research aims to develop new antibiotics to address this threat, as well as other potential biothreats such as Bacillus anthracis (carbon), Yersinia pestis (plague), Burkholderia mallei (glazes), and Burkholderia pseudomallei (meloidosis).

The collaborating institutions seek to address the growing antibiotic resistance among these common bacteria, with the goal of neutralizing the threat of antibiotic-resistant pathogens, both natural and those potentially engineered for malicious purposes.

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Francisella tularensis bacteria as a biological weapon

F. tularensis, the bacterium that causes tularemia, is primarily transmitted to humans by rodents and rabbits. Despite the small number of cases of tularemia (about 300 per year in the US), its potential as a biological weapon makes it a priority for research due to its high infectivity and morbidity. People affected with F. tularensis Experience symptoms such as skin ulceration, fever, cough, vomiting and diarrhea.

Dr. Kenneth Alibek, a former scientist involved in the Soviet Union’s bio-weapons program, revealed the use F. tularensis by the Soviet Red Army against German troops in the Battle of Stalingrad during World War II. The bacterium was also studied by Japanese microbial warfare research units and some Western militaries for military purposes, according to a summary from the American Journal of the Medical Sciences.

Current treatments for tularemia include antibiotics such as fluoroquinolones and aminoglycosides, but increasing levels of resistance require the development of new drugs.

To this end, USAMRIID has adopted a two-pronged strategy. The first involves locating critical targets within F. tularensis and discovery of inhibitors for these targets, with emphasis on the bacterium’s biomembrane, peptidoglycan and lipopolysaccharide structures.

The second strategy is a high-throughput screening of approximately 50,000 chemical compounds to find novel inhibitors, particularly against the live vaccine strain F. tularensiswhich is safe to handle in a Biosafety Level 2 laboratory.

The research team is currently characterizing several compounds to determine their effectiveness against fully virulent strains of the bacterium in more secure Biosafety Level 3 laboratories. These efforts also include evaluating the potential of these compounds against other bacterial threats.

The next phase involves testing the most promising compounds in a challenge model to assess their protective abilities against F. tularensis. Successful candidates will advance to further stages of development and potential clinical trials, contributing to the broader goal of protecting against current and future biological threats.

In 2009, the US Food and Drug Administration (FDA) granted orphan drug designation to a new antibiotic under investigation by the US Department of Defense as a potential prophylactic against deadly pathogens such as tularemia, anthrax and plague. The once-daily oral drug Restanza is being studied by Advanced Life Sciences as a potential biohazard countermeasure.

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