Six years ago, Michael Niederweis, Ph.D., described the first known toxin of the deadly pathogen Mycobacterium tuberculosis (Mtb), an exotoxin that had gone undetected for 132 years.

Mycobacterium tuberculosis bacteria/CDC

Now Niederweis and colleagues at the University of Alabama at Birmingham describe the mechanism of secretion and trafficking of that toxin, TNT, which is the major cytotoxicity factor for the pathogen that infects 9 million people a year and kills more than 1 million.

Their report, published in Nature Communications, identifies key secretion systems used by Mtb in pathogenesis, which makes them candidate targets for therapeutics.

When Mtb bacteria are inhaled into a human lung, they are engulfed by host lung macrophages and trapped inside intracellular vesicles called phagosomes. Mtb prevents the phagosome from merging with a lysosome, which otherwise would kill the bacteria. Instead, Mtb safely grows inside the phagosomes, then breaks out of the phagosomes into the cytosol of the macrophage, and it uses the TNT toxin to kill the macrophage by necroptosis, releasing the bacteria to infect other cells.

Read more at UAB