A breakthrough in labeling glycans holds promise for rapid tuberculosis diagnosis, enabling simpler and faster tests that could improve diagnosis and treatment outcomes.
Tuberculosis (TB), the world’s deadliest infectious disease, infects around 10 million people each year and kills more than 1 million annually. Once established in the lungs, the bacteria’s thick cell wall helps it to fight off the host immune system. Much of that cell wall is made from complex sugar molecules known as glycans, but understanding how these glycans help defend the bacteria has been a challenge due to their difficulty in being labeled.
A Breakthrough in Labeling Glycans
MIT chemists have now overcome this obstacle by developing an organic molecule that reacts with specific sulfur-containing sugars found only in three bacterial species, including Mycobacterium tuberculosis. These researchers were able to label the glycan ‘ManLAM’ using this tag and visualize where it is located within the bacterial cell wall.
Visualizing Glycan Dynamics
The researchers linked the oxaziridine tag to a fluorescent probe and showed that in Mycobacterium tuberculosis, this tag appeared in the outer layer of the cell wall. They also tracked the cells as they infected immune cells called macrophages and found that ‘ManLAM’ appears to remain in the bacterial cell walls for at least the first few days of infection.
Potential Diagnostic Implications
The ability to label glycans has significant implications for developing new diagnostics for tuberculosis. The current diagnostic test uses antibodies to detect ‘ManLAM’ in a urine sample, but it only works well in patients with very active cases of TB. The MIT team hopes to develop a more sensitive test that could detect ‘ManLAM’ in the urine even when only small quantities are present.
Future Research Directions
The researchers now plan to use this approach to study what happens to the bacteria following treatment with different antibiotics, or immune stimulation of the macrophages. They also hope to create new diagnostics for tuberculosis and better understand how the bacterial cell wall is assembled and how ‘ManLAM’ helps bacteria get into macrophages and other cells.
Conclusion
This breakthrough in labeling glycans could lead to simpler, faster tuberculosis tests, which would be especially beneficial in developing nations where TB rates are high. The development of a more sensitive test that can detect small quantities of ‘ManLAM’ in the urine could improve diagnosis and treatment outcomes for patients with TB.
Tuberculosis (TB) diagnosis involves a combination of medical history, physical examination, and laboratory tests.
A chest X-ray is often used to visualize lung damage.
Sputum smears are examined under a microscope for the presence of Mycobacterium tuberculosis bacteria.
Blood tests may also be conducted to detect TB antibodies.
The World Health Organization (WHO) recommends a comprehensive approach to diagnose TB, including clinical evaluation and laboratory confirmation.
