Promising protein discovered for new drugs against tuberculosis

Zebrafish embryos

It was recently discovered that immune cells can destroy bacteria by, as it were, eating them. They do so when there is a risk of bacterial outbreak. But so far researchers did not know how this process was triggered. Leiden PhD candidate Michiel van der Vaart discovered that in infected zebrafish embryos DRAM1 stimulates the process by which macrophages 'eat' the bacteria.

Selective breakdown

What is essential in this context is that the DRAM1-driven breakdown is selective: the process focuses specifically on the bacteria and not on properly functioning cell constituents. In the zebrafish embryos, it works without side effects. It turns out that DRAM1 is also active with the tuberculosis bacteria in human macrophages. Together with Tom Ottenhoff's LUMC group, Meijer wants to try to strengthen the immune pathway via DRAM1. This would provide a starting point for developing new drugs against tuberculosis. Their article on the subject is due to appear in Cell Host & Microbe on 11 June.

Parasite

The tuberculosis bacteria, Mycobacterium tuberculosis, misuse our immune system. When bacteria penetrate our body, the macrophages are responsible for removing them. These immune cells absorb pathogens to kill them. But the tuberculosis bacteria escape this attack and have even found a way to survive in the macrophages as a parasite.

On the other hand, the macrophages do take the bacteria hostage. 'Macrophages are able to keep the bacteria in check and in this way to control the infection,' says biologist Annemarie Meijer.

Zebrafish

Her group is investigating this process in zebrafish embryos. The fish can be infected by Mycobacterium Marinum, a close relative of the tuberculosis bacteria. In order to find out how the macrophages of infected embryos recognise the bacteria and activate the immune response, Meijer's group went in search of proteins that are produced in greater numbers during an infection. They identified a number of these, of which the protein DRAM1 seems to be most promising.