MIT Chemists Develop New Method to Visualize Tuberculosis Glycans

Tuberculosis (TB) remains a leading infectious disease worldwide, responsible for over a million deaths annually and infecting around 10 million people each year. The bacteria’s survival is aided by a thick cell wall, largely composed of glycans. However, the specific roles these glycans play in protecting the bacteria, particularly in evading the human immune system, have been difficult to study due to the lack of effective methods for labeling and tracking them inside cells.

MIT chemists have now addressed this challenge by developing a labeling technique for a glycan called ManLAM, which is found in the cell walls of Mycobacterium tuberculosis. They used an organic molecule that selectively reacts with sulfur-containing sugars unique to only a few bacterial species, including M. tuberculosis. By attaching a fluorescent probe to this molecule, the researchers could specifically label ManLAM and observe its location within the bacterial cell wall. This allowed them to track the glycan during the first days of infection in host immune cells.

The team’s method is notable because glycans are generally hard to label, lacking the distinctive sequences or chemical reactivities that make proteins and DNA easier to tag. This new approach enables researchers to visualize a single glycan with high specificity. Importantly, the researchers found that, contrary to some hypotheses, ManLAM largely remains attached to the bacterial cell wall during early infection, rather than being shed and interacting directly with the host immune system.

The researchers hope that this labeling technique will not only improve understanding of TB’s biology but also lead to better diagnostic tests. Current diagnostics, such as sputum cultures, can be slow and unreliable, especially for children and in resource-limited settings. The MIT team is exploring whether their labeling method could be adapted to detect TB glycans in urine, potentially offering a faster, simpler, and more sensitive alternative to existing tests.

“There aren’t a lot of good diagnostic options, and there are some patient populations, including children, who have a hard time giving samples that can be analyzed. There’s a lot of impetus to develop very simple, fast tests,” says Laura Kiessling, senior author of the study published in the Proceedings of the National Academy of Sciences.