Insight: Research Edition

Fall 2005

Past Biological Weapons Raise Concerns

In the Australian outback, in the rice paddies of Thailand and in the fields of Cambodia, a deadly bacterium awaits the rainy season to begin its killing spree. No vaccine can protect its human victims. It can lie dormant in human cells for decades. It can take a life within 48 hours without ever being detected and, even when diagnosed properly, it is resistant to many of the most powerful antibiotics known to man.

If the disease melioidosis doesn’t sound familiar, don’t feel alone. This tropical infection has largely been off the radar of researchers in the United States. But that is changing. Dr. Herbert Schweizer, a Professor in the Department of Microbiology, Immunology and Pathology, is at the scientific front lines of research into the pathogen that causes melioidosis, thanks in large part to its identification as a “select agent” for bio-terror by the National Institute of Allergy and Infectious Diseases.

“Burkholderia pseudomallei is on the select agent list because of its potential for use as a biological weapon,” said Dr. Schweizer. “A close relative, B. mallei, has been used in biowarfare before, so there is a precedent. NIAID is concerned that B. pseudomallei could be targeted for weaponization and wants to take steps to protect public health by developing better diagnostic tools and therapeutic agents.”

During World War I, horses and mules were the primary mode of military and civilian transport. If you could take out your enemy’s transportation, you had a better chance of taking out your enemy and that is just what the Central Powers attempted to do. Glanders, which is caused by the bacterium B. mallei, is a disease that kills horses and, more rarely, people. The disease was spread by German troops to infect large numbers of Russian horses and mules on the Eastern Front. But that was only the beginning. The bacterium was used by the Japanese during WWII to infect civilians, horses and prisoners of war. The United States and the former Soviet Union also studied B. mallei as a potential weapon of biological warfare during and shortly after the war. Because of its persistence in the environment and its much greater drug resistance, B. pseudomallei is now seen by many as an equal or perhaps even likelier tool of terror.

Today, Dr. Schweizer is con-ducting research to develop a better understanding of B. pseudomallei’s resistance to antibacterials, and how new drugs may overcome that resistance enabling melioidosis to be effectively treated with existing antibiotics. Because B. pseudomallei evolved in the soil with organisms that secrete antibacterial compounds, it has developed mechanisms to protect itself.

“What we are looking at is the function of efflux pumps that basically work to pump antibacterials, which include many of the commonly used antibiotics, out of the bacterium before the compounds can do any damage,” said Dr. Schweizer. “If antibiotics can’t stay in the bacterium, they won’t be effective in stopping infection. If we can find inhibitors that will stop the action of these pumps, we may be able to develop an inhibitor-drug co-therapy that will allow use of many of the antibiotics that currently cannot be used because they are effluxed.”

In addition to work on efflux pumps, researchers at the Regional Center of Excellence for Biodefense and Emerging Infectious Diseases are developing vaccines and rapid diagnostic tools to either prevent the disease altogether or at least improve the outcomes of medioidosis treatments. They also will develop public health programs to create awareness of the disease and its symptoms. The focus on B. pseudomallei can’t come soon enough for regions of the world that have struggled in isolation to fund even basic research into melioidosis, let alone develop effective drug therapies. Australia, because of a medical infrastructure that allows for quick diagnosis and intensive long-term treatment with high compliance rates, has reduced the death rate from the disease to less than 20 percent. But in developing countries, with few medical facilities and even fewer monetary resources to sustain expensive treatment, the death rate remains at 50 percent. Now, thanks to NIAID funding, that picture could change. Dr. Schweizer notes that some have criticized the government’s investment in bioterrorism as a drain on biosciences, but researchers will be learning a lot and that is a good thing.

“Even if we never have a bioterror attack using B. pseudomallei, this research will benefit so many who suffer from the consequences of infection by this pathogen,” said Dr. Schweizer, who has traveled to Australia and Singapore to conduct field research and develop a greater understanding of melioidosis. “People who have worked with the disease for so many years have felt that they were alone in the wilderness. Now, with NIAID funding and the resources of the Regional Center of Excellence at CSU, they finally have hope that they one day can offer their patients readily accessible and much more affordable life-saving therapy.”