Study shows how tuberculosis sugars interact with mammalian receptors

Researchers have synthesized 60 glycans representative of all the classes of carbohydrates found on the tuberculosis bacterium and screened them against some human receptor proteins. By probing the way these glycans and proteins interact, the study provides insights into molecular mechanisms that enable TB bacteria to invade human cells and survive there during infections. Glycans found on surfaces of mycobacteria, the group to which the TB bacterium belongs, are known to cause host immune responses, but it has been difficult to profile the host proteins, called lectins, that recognize these sugars. Hypothetically, the glycans could be made enzymatically or isolated from bacteria. But most enzymes that make them are not known, and isolated glycans are hard to purify and characterize and lack linkers needed to immobilize them on arrays. Todd L. Lowary of the University of Alberta and coworkers therefore chemically synthesized the 60 representative glycans with linkers, attached them to bovine serum albumin, and printed them on glass slides. The team, also including the groups of Maureen E. Taylor and Kurt Drickamer at Imperial College London, then screened the resulting array with a panel of fluorescently labeled carbohydrate-recognition fragments from one cow lectin and several human lectins (ACS Chem. Biol. 2017, DOI: 10.1021/acschembio.7b00797). Among other results, screening revealed binding of the mannose receptor and the protein DC-SIGN to two families of TB glycans, interactions that promote entry of the mycobacteria into immune-system macrophages.