A simple strategy for detecting tuberculosis

Tuberculosis afflicts more than 9 million people annually, according to the World Health Organization. A key step to keeping TB in check is to detect and monitor the disease to ensure patients aren’t developing resistance to their medication. In wealthy areas, this is done with chest X-rays and advanced lab tests. In resource-strapped regions, where TB can be common, patients are typically diagnosed with the Ziehl-Neelsen test—an 11-step saliva screening that dates back to the 1880s. Now, researchers led by Stanford University’s Carolyn Bertozzi report they can diagnose TB with a simpler procedure. The new test relies on a dye called 4-N,N-dimethyl­amino-1,8-naphthalimide, or 4-DMN. This dye changes color in response to its surroundings: It’s colorless in aqueous solutions but glows green in hydrophobic environments. Bertozzi’s group covalently linked 4-DMN to the disaccharide trehalose. An enzyme in Mycobacterium tuberculosis adds a long fatty acid chain to the 4-DMN-trehalose molecule, which then becomes integrated into the microorganism’s hydrophobic membrane, where it glows. Because the bacterium must be alive to metabolize the molecule, the new procedure doesn’t detect dead cells, making it a good point-of-care test for following TB’s progress. The diagnostic procedure, Bertozzi said, is very simple: A solution of 4-DMN-trehalose is combined with a saliva sample, incubated for about an hour, and then observed with a microscope. “We don’t even have to wash it,” she noted. The compound is currently being field-tested in South Africa in collaboration with Bavesh Kana of the University of the Witwatersrand.