Lab-Made Sugars Aid Diagnosis

A new oligosaccharide synthesis could lead to more reliable diagnoses of the bacterial disease brucellosis, which afflicts animals and people worldwide.

When cattle are infected with Brucella bacteria, infection can spread rapidly within herds, where it causes abortion, births of weak calves, and reduced milk yields. In people, who can catch brucellosis from unpasteurized dairy products or contaminated meat, symptoms include excessive sweating and joint and muscle pain, and the condition can be chronic or even lifelong.

Brucellosis is typically diagnosed by detecting antibodies the body produces to fight the bacteria. But the Brucella cell-wall molecule contains two oligosaccharide antigens, A and M; other bacteria carry the same A antigen; and antibodies to A and M cannot currently be detected independently. So brucellosis diagnostic tests often give false-positive results, which complicate human treatment and cause commercial animal herds to be declared disease-tainted when they’re not.

Now, David Bundle of the University of Alberta; John McGiven of the Animal & Plant Health Agency, in Surrey, England; and coworkers have synthesized several versions of Brucella antigens and have conjugated them to carrier proteins (J. Am. Chem. Soc. 2014, DOI: 10.1021/ja5081184). The conjugates can bind and detect A and M antibodies independently. The researchers suggest that the disaccharide M-antigen conjugate could be used to unambiguously detect the immune response to brucellosis infection in humans and animals.

“We have established collaborations to evaluate the synthetic antigens for diagnosis,” Bundle says.

Brucellosis expert Jacques Godfroid of the University of Tromsø—the Arctic University of Norway, says, “For the brucellosis scientific community and all those fighting brucellosis—farmers, veterinary services, and food safety and veterinary public health scientists—this work represents the first major breakthrough in decades toward avoiding false-positive serological reactions in brucellosis testing. A test would have to go through validation steps, but for the first time in decades there is something extremely promising.”