Here, with the support of a recently awarded $458,000 National Institutes of Health grant, Caswell studies the elusive activities of a bacterium called Brucella. Unlike other bacterium, Brucella is able to sneak like a spy into the body’s immune cells, causing abortions and sterility in animals and a debilitating flu-like disease in humans.
Each year, Brucella infects approximately 500,000 people worldwide. It is often contracted from animals through direct contact or consumption of unpasteurized dairy products, putting veterinary and other animal workers most at risk. There is no vaccine to prevent infection in humans.
“With this latest grant, we will examine the unique genetic circuitry of Brucella, and how it allows the bacterium to trick, invade, and live inside immune cells,” said Caswell, an assistant professor of bacteriology in theVirginia-Maryland College of Veterinary Medicine and a Fralin Life Science Institute affiliate. “If we can figure out exactly how Brucella accomplishes infection, we could develop an effective drug.”
Specifically, Caswell is looking at a transcriptional regulator that activates the expression of four genes important to Brucella’s ability to cause disease. To date, the regulator and genes have not been characterized, making them a ripe area for further exploration, according to Caswell.
“Brucellosis is a neglected disease of poverty that needs a ‘One Health’ approach,” said David O’Callaghan, director of Unit 1047 of the French National Institute of Health and Medical Research, known as Inserm, at the Université de Montpellier in Nîmes, France.
“Clay Caswell’s novel work is mapping uncharted waters, characterizing novel pathways of gene expression that allow this stealth pathogen to infect animal and human hosts and cause disease,” O’Callaghan said. “This is an essential step for the design of new diagnostic tests and vaccines.”
Brucella packs a potent punch — only a small dose of 10 to100 bacteria can cause infection. While it can be treated with antibiotics, it can take up to eight weeks to clear. In some cases, Brucella can infect the heart’s inner lining and, if untreated, destroy the heart valves, resulting in death.