By David Kipkorir
New research has investigated the structure of a natural self-destructive mechanism contained in the bacterium that causes tuberculosis (TB) in humans.
Researchers are currently seeking to apply this ‘suicide’ mechanism for therapeutic purposes.
Using the new findings may soon lead to better treatment outcomes.
The researchers identified one ‘toxin-antitoxin’ (TA), termed Mycobacterium tuberculosis (MbcT), with a more dramatic effect – in the absence of the antitoxin the toxin kills the bacteria.
This effect flagged MbcT’s potential as a drug target and led the team, headed by Annabel Parret, staff scientist at the European Molecular Biology Laboratory (Hamburg, Germany), to try and understand its structure.
“Our goal was to see the TA system’s structure, so we could try to understand and even manipulate it. It was as if we were working blindly before,” said Parret.
The high-resolution structure revealed a large and compact system with a double doughnut shape, and this knowledge gave important guidance for further studying the system’s biochemistry.
The researchers were able to understand MbcT’s mode-of-action; without the antitoxin, the toxin starts to degrade the important cellular molecule NAD+, a ‘suicide’ mechanisms ultimately leading to the death of the cell.
“Our collaborators in France were already able to extend the lifetime of mice infected with TB by activating the toxin in a controlled way,” added Parret. “If we find molecules that can disrupt the TA system – and thus trigger cell death – in TB patients, that would be the perfect drug.”
The team now hopes to screen small molecules for this capability, and identify a potential drug target.
In the Kenya, more than 29, 000 people died of tuberculosis in 2017, according to World Health Organisation (WHO).
The Ministry of Health reports that 138, 105 people contract TB every year.
WHO estimates that approximately 10 million people had TB in 2017, and that 1.6 million people died as a result.
The UN health agency noted that many people suffering from TB do not know it as it continues to be the top infectious killer worldwide, claiming over 4,500 lives a day.
WHO is calling on all stakeholders and partners to take unprecedented and bold action to advance efforts to end TB and AIDS by 2030.
According to Kenya’s National Tuberculosis, Leprosy and Lung Disease Program, the major factor responsible for the large TB disease burden is the concurrent HIV epidemic.
Tuberculosis is a curable and preventable disease caused by bacteria (Mycobacterium tuberculosis) that most often affect the lungs.
TB contains 80 toxin–antitoxin systems (TAs), sets of closely linked genes that encode a toxic protein and an antitoxin.
When the bacteria are growing normally, the toxin’s activity is blocked by the antitoxin’s presence.
However, under stressful conditions the antitoxin molecules are degraded, activating the toxin and slowing the growth of the bacteria, allowing them to survive the stressful environment.
In Kenya World TB Day is observed on 24 March every year to raise public awareness regarding the epidemic of TB and efforts of eliminating the disease.
It commemorates the day in 1882 when Dr. Robert Koch astounded the scientific community by announcing that he had discovered the cause of tuberculosis, the TB bacillus.