Imagine a serial killer travelling across provinces, attacking the young and old, healthy and sick, rich and poor, with increased confidence that they haven’t been stopped yet.
One day they arrive in a new place and identify a new target to attack and kill. However, this time they have chosen someone who is ready and willing to put up a fight. They are subdued, taken into custody by the police and imprisoned. However, they are quick to make a prison break by damaging the walls of their prison cell and thus are able to escape. Not long after this, after triggering the alarm system, they are surrounded by snipers with their lasers pointed at their arms, legs, chest and head until reinforcements arrive. They are sentenced to death and locked up in prison until then. Finally, when the day of their death penalty arrives no one is sad to see them go and the people affected are overcome with a feeling of relief.
Mycobacterium tuberculosis (M. tuberculosis) is the bacterium responsible for infecting people and causing tuberculosis (TB) through aerosol droplets and infects millions of people annually around the world. And so, if we read the above story in the context of M. tuberculosis infection and TB, it reads as follows…
Imagine a serial killer bacterium travelling across provinces, attacking the young and old, healthy and sick, rich and poor, with increased confidence that they haven’t been stopped yet due to their ability to resist the action of anti-TB drugs, termed acquired drug resistance. This bacterium is M. tuberculosis.
One day they arrive in a new place and identify a new target to attack and kill the bacterium infects a new host. However, this time they have chosen someone who host’s immune system, the first defence of the host against an infecting bacterium, is ready and willing to put up a fight. they are subdued, taken into custody by the police and imprisoned This results in the bacterium being engulfed by the phagosome, a vesicle formed around an intracellular bacterium to contain it and prevent it from further infecting the host. However, they are quick to make a prison break by damaging the walls of their prison cell and thus are the bacterium is able to rupture the walls of the phagosome, enabling its escape. Not long after this, after triggering the alarm system the bacterium’s escape from the phagosome triggers the host’s immune system and they are surrounded by snipers with their lasers pointed at their arms, legs, chest and head the bacterium is surrounded by ubiquitin, a small protein responsible for tagging other proteins, organelles, and intracellular pathogens for degradation, attached at specific target proteins aided by an E3 ubiquitin ligase enzyme. until reinforcements arrive The surrounding of the bacterium by ubiquitin recruits autophagy adaptors (known as LC3, p62, NBR1, NDP52 and optineurin) to aid this process, They are sentenced to death and locked up in prison until then preventing the replication of the bacterium and allowing the killing of the bacterium. Finally, when the day of their death penalty arrives no one is sad to see them go and the people affected are overcome with a feeling of relief. Finally, once the phagosome has closed, it binds with the lysosome, a degradative cellular compartment that breaks down proteins, and the bacterium is destroyed. This process is called xenophagy, and in this way the host immune system fights the TB infection.
However, the specific M. tuberculosis proteins to which the ubiquitin attaches (the arms, legs, chest and head of the serial killer) is unknown and M. tuberculosis has also developed novel ways to hijack this system to use it for its own benefit. In an effort to further our understanding of the host’s immune response to intracellular M. tuberculosis infection, the aim of my project is to identify the proteins tagged with ubiquitin and the E3 ubiquitin ligase enzymes involved in this process using computer and laboratory techniques.
