The pathogen causing tuberculosis disease, Mycobacterium tuberculosis (Mtb) is the second leading cause of death from a single infectious agent globally, behind COVID-19. Mtb infected 10 million and killed 1.5 million people in 2020. Part of Mtb’s success is due to the bacteria’s ability to modulate its macrophage host. Detecting infected individuals is challenging due to some 90 % of individuals being infected but clinically silent (e.g. latent infection), while Mtb’s intracellular nature makes detecting host cells equally challenging. As such new targets are needed for disease detection and elimination.
Most cellular processes, including host-pathogen interactions during Mtb invasion, infection, and survival, are controlled by proteins. Here, the promising but underrepresented sub-field of plasma membrane proteomics is exploited. It was hypothesized that the surface of the host macrophage itself may be modulated during Mtb infection.
Using the virulent Mtb strain H37Rv to infect primary human macrophages, differences in plasma membrane proteomic signatures were quantified compared to controls. This is, to our knowledge, the first time the plasma membrane proteome has been quantified using label-free mass spectrometry.
These protein hits will now be taken forward to better characterise Mtb driven changes to host cells and may lead to biomarkers of Mtb infection, including detection of clinically silent or ‘latent’ infection.