Researchers from the University of Warwick in the United Kingdom have discovered a new enzyme structure in the bacteria Mycobacterium tuberculosis (Mtb) that causes TB, which they say could help them to design unique drugs to fight the disease.
A team of researchers led by Dr. Elizabeth Fullam, has revealed that the discovery of the structure of the enzyme N-acetylglucosamine-6-phosphate deacetylase (NagA) will enable scientists to inhibit this critical pathway and kill TB.
Whereas translating the findings of the study into actual drugs might take some years, they represent good news for millions of people in Uganda and several other countries that are battling the scourge of TB.
According to the 2015 Uganda National Tuberculosis Prevalence Survey, some 90,000 tuberculosis cases are registered every year. The 2016 Global Tuberculosis Report also found that only 43,736 TB cases (49%) were identified in Uganda in 2015.
TB causes more deaths than any other infectious disease, including from HIV and malaria. In 2016 there were 10.4 million new cases of TB and 1.7 million people died. The rise in cases of TB that are resistant to the current therapies that are available means that there is an urgent need to develop new TB therapeutics.
Scientists note that Mtb, the bacteria that causes TB is a highly unique organism that is enclosed within a distinctive cell wall comprised of unusual sugars and lipids which protect the bacteria from the host environment.
Researchers argue that knowledge of the chemical environment including the enzymes, could help them to design drugs that can disrupt the cell wall leading to the death of the bacteria.
The researchers used highly powerful X-ray facilities at the Diamond Light Source, Harwell, that provided detailed molecular insights into how the NagA enzyme generates important precursors that are involved in Mtb cell wall biosynthesis and metabolism.
Dr Fullam, who is a Sir Henry Dale Fellow at the University of Warwick’s School of Life Sciences, said: “Tuberculosis is a major global health problem and the current drugs that we use today are over 40 years old. It is therefore vital that we discover new therapeutic agents to combat TB.
In our studies, we have investigated the role of an enzyme in Mtb called NagA. This enzyme is a promising drug target as it is at a crucial metabolic chokepoint in Mtb. This means that a molecule that stops the enzyme from working would be an effective strategy for a drug and therefore it is critical to understand its function.
She added: “Our group has identified a weak point within this protein that we can target and will now enable us to design specific molecules to block its function.”
