Researchers have developed a method to label specific sugars, or glycans, on the surface of Mycobacterium tuberculosis (Mtb) by targeting a rare chemical feature. This approach offers a potential new avenue for tracking and understanding key bacterial components involved in the world's deadliest pathogen – and future diseases.
The study, published in PNAS, focuses on methylthioxylofuranose (MTX), a rare sugar which is found in certain mycobacterial pathogens. MTX is part of mannose-capped lipoarabinomannan (ManLAM), a molecule on the surface of Mtb that affects how the immune system responds to infection. A thioether group – a chemical feature that is unusual in sugars – on MTX enables selective labeling using oxaziridine-based reagents.
The team demonstrated that oxaziridine probes can react with the MTX thioether in vitro and in living cells, enabling site-selective labeling of MTX-containing glycans. The labeling was specific to Mtb and did not occur in non-harmful mycobacteria. Using this technique, they were able to see where ManLAM was located in bacteria and in infected immune cells, using fluorescence microscopy.
The labeling approach proved specific despite the presence of other sulfur-containing molecules, such as methionine in proteins. This chemical precision is critical for downstream diagnostic applications, where nonspecific signals can lead to false results.
This study also highlights this method's potential to support the development of new diagnostic tools that detect Mtb directly in samples like tissue or sputum. Unlike tests that rely on detecting immune responses or bacterial DNA, this approach could provide more direct and localized information about where bacteria are active during infection.
While this study focused on proof-of-concept labeling and visualization, the authors note that it could be adapted for use in clinical samples and potentially expanded to other bacterial studies. The unique chemical reactivity of MTX could also be applied to broader applications, such as designing new diagnostic or research tools related to glycan biology and infectious disease.
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