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Researchers Find Clue to How M. Tuberculosis Replicates

Discovery seen as possibly leading to new anti-TB drugs

New drugs to treat resistant strains of TB are now a possibility, according to researchers from the University of Surrey in England.

The researchers identified the source of nitrogen in host blood cells that allows the pathogen Mycobacterium tuberculosis to make proteins and DNA. Preventing access to nitrogen will stop the TB bacillus from growing inside blood cells.

The researchers developed a new computational technique called 15N-Flux Spectral Ratio Analysis (15N-FSRA) to learn more about nitrogen metabolism. 15N is a non-radioactive isotope of nitrogen that can be tracked by mass spectrometry. In the first step of the study, blood cells were fed with different potential nitrogen sources labelled 15N, enabling observation. The cells were then infected with TB bacillus and allowed to replicate and take nitrogen from the host cell. Protein from both blood cells and TB cells were recovered, which meant the researchers could track the route by which the 15N went from host cell to TB bacillus.

The researchers discovered that TB bacillus acquires most of its nitrogen from the host cell amino acid, glutamine. a critical part of the immune system.

The discovery could lead to new anti-TB drugs that target the transportation and metabolism of glutamine in the body, which will prevent M tuberculosis from accessing the nitrogen it needs to survive and replicate.

Johnjoe McFadden, professor of molecular genetics at the University of Surrey, said, “Our finding paves the way for the development of [drugs that] can target uptake of the very amino acid that enables the bacteria to replicate and spread within the body.”

Source: University of Surrey, December 4, 2019

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