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Infectious disease

Tuberculosis-causing bacterium produces antacid that may help bug persist

Compound raises pH and short-circuits macrophages’ killing process

by Celia Henry Arnaud
August 24, 2019 | APPEARED IN VOLUME 97, ISSUE 33

 

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Unlike most bacteria, the pathogen that causes tuberculosis—called Mycobacterium tuberculosis—has a years-long cycle of infection. Scientists haven’t discovered what gives M. tuberculosis its staying power. Five years ago, a team led by D. Branch Moody of Harvard Medical School identified a compound that’s unique to M. tuberculosis, the lipid 1-tuberculosinyladenosine (1-TbAd). Moody wondered whether 1-TbAd might help the pathogen persist inside phagosomes, compartments within macrophages, a type of immune cell. Moody and his colleagues now report that 1-TbAd acts as an antacid that raises phagosomes’ pH and makes them swell. These changes disrupt the processes macrophages would otherwise use to kill the bacteria (Nat. Chem. Biol. 2019, DOI: 10.1038/s41589-019-0336-0). Tests with 1-TbAd and analogs showed that the compound’s activity depends on the location of the lipid linkage at the 1 position of adenosine. N6-TbAd, which has a different lipid linkage, doesn’t have the same effect on pH. Because the researchers found 1-TbAd in 50 out of 52 clinical strains of M. tuberculosis they tested, they suspect that it could be used to detect tuberculosis in patients. They are working on developing tuberculosis diagnostics based on the compound, Moody says.

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