The first probe that can light up Mycobacterium tuberculosis while the pathogen lives inside macrophage cells has been developed by a research team led by Benjamin G. Davis of Oxford University and Clifton E. Barry III of NIH’s National Institute of Allergy & Infectious Diseases. The so-called fluorescein-containing trehalose probe could form the basis of a diagnostic tool for detecting tuberculosis infection and monitoring treatment (Nat. Chem. Biol.,DOI: 10.1038/nchembio.539). Tuberculosis claims nearly 2 million lives annually, but to date the bacterium could be visualized only after it was dead by using complicated staining methods. To build a successful live-cell probe, the team co-opted enzymes that the pathogen uses to install essential lipid-modified variants of trehalose disaccharides into its cell wall. The researchers first established that the enzymes could still operate with fluorescently modified trehalose molecules and then showed that the flickering sugar was snugly embedded in the bacterial cell wall. “Our findings arm tuberculosis biologists with the first fluorescent small-molecule probe to label M. tuberculosis not only in culture but also in infected macrophages,” the researchers write.