New Drug Therapies For Asymptomatic TB In The Pipeline

Active and asymptomatic (latent) tuberculosis infections may be soon find a cure in recent drug therapies that are being developed by researchers at the University of Maryland. They hope to combat M. tuberculosis (the bacterium causing the disease) by characterizing the unique structure and mechanism of an enzyme in it.

"The NAD+ synthetase enzyme that our study describes is absolutely essential for the survival of the tuberculosis bacteria and an important drug target. We can now use the information we have about its structure and mechanism to develop inhibitors for this enzyme," Nature magazine quoted Barbara Gerratana, an Assistant Professor of Chemistry and Biochemistry, whose research team included graduate student Melissa Resto and Assistant Professor Nicole LaRonde-LeBlanc, as saying.

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The researchers point out that NAD+ synthetase is responsible for making NAD+, a coenzyme found in all living cells that is involved in regulating many cellular processes and in reduction-oxidation metabolic reactions.

They say that more than one biosynthetic pathway is usually involved in NAD+ production.

In humans, according to the team, NAD+ can be obtained through several different complex pathways, and not all of the pathways utilize NAD+ synthetase to produce NAD+.

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However, there are only two pathways involved in producing NAD+ in the tuberculosis bacterium, and both depend on the activity of NAD+ synthetase to obtain NAD+.

"We are optimistic about the potential for developing new drugs that will effectively target this enzyme in TB and minimize side effects to humans, since we have NAD+ biosynthetic pathways that are independent of the NAD+ synthetase activity," Gerratana said.

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Current treatment of tuberculosis targets the active tuberculosis bacterium, and has little effect on the non-replicating bacterium.

"If we don't tackle latent tuberculosis, this disease will not be eradicated," Gerratana said.

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A research article on the researchers' observations has been published in the journal Nature Structural and Molecular Biology.

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