Researchers at the Massachusetts Institute of Technology (MIT) have made significant strides in tuberculosis (TB) testing by developing a new molecular labeling technique. Professor Laura Kiessling, Novartis Professor of Chemistry at MIT, is at the helm of an exciting development. Their mission is to make the diagnosis of Mycobacterium tuberculosis, the bacteria that causes TB, faster and easier.
Diagnosing TB today takes at least two weeks. This multi-month process is a result of the time it takes for the bacteria to cultivate in lab environments. The recently published study aimed to identify ways of taking advantage of Mycobacterium tuberculosis’ unique characteristics to develop diagnostic tests that are faster and more effective.
Understanding Mycobacterium tuberculosis and Its Glycans
Mycobacterium tuberculosis has an unusual sugar in its cell wall, called MTX. This sugar has a thioether, meaning there’s a sulfur atom snuggled up between two carbon atoms. This bacterium is equipped with an important glycan, ManLAM, as a prominent feature on its outer surface. Glycans, like ManLAM, are extremely important for cellular communication. They have a profound effect on the way bacteria interact with host immune cells.
These glycans are some of the hardest to label for the simple reason that they don’t have defining chemical sequences, or reactivities, that an artist can easily go after. Kiessling points to the most important point: there is a lack of good diagnostic options. Moreover, some patient populations, including children, find it difficult to produce samples for testing. There is huge pressure to create extremely easy, quick tests.
The ManLAM coats the surface of Mycobacterium tuberculosis and helps the bacterium evade the host immune system and survive. It shapes the type and degree of immune response elicited by host immune cells. Stephanie Smelyansky, a researcher involved in the study, highlights this interaction: “Something that’s often underappreciated is the fact that these glycans can interact with our host cells. When our immune cells encounter these glycans, they don’t trigger a danger alert. Rather, they communicate that nothing is amiss and all is well.
Innovative Labeling Technique
Researchers realized that labeling glycans in the bacterium Mycobacterium tuberculosis presented more challenges. To address this problem, they created an approach which conjugates an oxaziridine to a fluorescent reporter. Thanks to this novel approach, scientists now have an opportunity to image particular glycans found on the surface of this bacterium.
The labeled glycan was indeed identified in the outer layer of the cell wall of Mycobacterium tuberculosis. Remarkably, this labeling lasts for up to 72 hours, allowing for significant long-term analysis. Kiessling emphasized the importance of this technique, stating, “Having a handle to follow the bacteria is really valuable, and it will allow you to visualize processes, both in cells and in animal models, that were previously invisible.”
This discovery represents a significant advance in our understanding of Mycobacterium tuberculosis. It clears the path for creating more simplified diagnostic tests that would transform how we detect TB.
Implications for Tuberculosis Diagnostics
The implications of this research are profound. Increased speed of diagnosis by making testing easier to perform would mean earlier treatment, and from that, the stoppage of tuberculosis’ spread could be realized. The current approaches heavily favor culture-based methods which are not amenable for rapid response, particularly when time matters in vulnerable populations.
Researchers are focusing on glycans such as ManLAM. Their goal is faster, more accurate tests. The ability to visualize these glycans is an important leap ahead. This ongoing work is important for understanding how the newly described bacterium acts and evades mammalian host immune systems.
“Having a handle to follow the bacteria is really valuable, and it will allow you to visualize processes, both in cells and in animal models, that were previously invisible.”
