Mechanisms of tuberculosis pathogenesis

Tuberculosis (TB), humanity’s single greatest infectious killer, is estimated to have claimed a billion lives.

Despite more 70-years of effective antibiotics and 100-years since the BCG vaccine was introduced, TB remains the greatest infectious killer, causing disease in 10 million people and killing 1.3 million in 2022.

This is because several months of treatment with multiple antibiotics are required for cure, which is difficult for people to adhere to particularly in deprived areas of the world.

Moreover, while the BCG vaccine offers some protection to children, protection does not last into adolescence and adulthood. These findings highlight that TB bacteria have learned to evade both our immune defences and antibiotics. Completely new scientific approaches are needed to find new treatments and vaccines.

We have developed the tiny zebrafish larva as a model in which to study TB. The larvae are transparent, so we can infect them and watch disease occur under the microscope. We can determine which host defences the bacteria are evading.

Moreover, by engineering zebrafish with heightened susceptibility to TB, we can understand why some individuals can resist TB while cannot.

Our work is informing completely new treatments for TB and some of our findings have been found to be relevant for human TB sufferers.

Finally, we are trying to understand why the TB bacteria are so difficult to treat with antibiotics with the hope to be able to shorten and simplify TB treatment.