Researchers from the Defense Threat Reduction Agency (DTRA), United States Army Medical Research Institute of Infectious Diseases (USAMRIID), and 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 tularemias, Francisella tularensis, is designated as a Tier 1 select agent, “presenting the greatest risk of deliberate misuse with most significant potential for mass casualties”, marking it as a potential biological weapon, according to a release from the DTRA’s Chemical and Biological Technologies Department on 6 January 2024.
The initiative between the DTRA, USAMRIID and Walter Reed Army Institute of Research intends to develop new antibiotics to counter this threat, as well as other potential biothreats including Bacillus anthracis (anthrax), Yersinia pestis (plague), Burkholderia mallei (glanders), and Burkholderia pseudomallei (melioidosis).
The partnered institutions seek to address increasing antibiotic resistance among these common bacteria, aiming to counteract the threat of antibiotic-resistant pathogens, both naturally occurring and those possibly engineered for malicious purposes.
Francisella tularensis bacteria as a bioweapon
F. tularensis, the bacterium causing tularemia, is primarily transmitted to humans from rodents and rabbits. Despite the low number of tularemia cases (about 300 annually 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 including skin ulcer, fever, cough, vomiting and diarrhoea.
Dr. Kenneth Alibek, a former scientist involved in the Soviet Union’s bio-weapons programme revealed the use of 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 germ warfare research units and some of the Western military powers for military purposes, according to an abstract from the American Journal of the Medical Sciences.
Current treatments for tularemia include antibiotics like fluoroquinolones and aminoglycosides, but rising resistance levels necessitate the development of new drugs.
To this end, USAMRIID has adopted a dual strategy. The first involves identifying critical targets within F. tularensis and discovering inhibitors for these targets, with a focus on the bacterium's biofilm, peptidoglycan, and lipopolysaccharide structures.
The second strategy is a high-throughput screening of about 50,000 chemical compounds to find new inhibitors, particularly against the Live Vaccine Strain of F. tularensis, which is safe for handling in a Biosafety Level 2 laboratory.
The research team is currently characterising 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 capabilities against F. tularensis. Successful candidates will advance to further development stages and potential clinical trials, contributing to the broader goal of safeguarding against current and future biological threats.
In 2009, the US Food and Drug Administration (FDA) granted orphan drug designation to a novel antibiotic under research by the US Department of Defense as a potential prophylactic against lethal pathogens including tularaemia, anthrax and the plague. The once-daily oral drug, Restanza, was studied by Advanced Life Sciences as a potential biohazard countermeasure.
