Toxins from a Newly Made Tuberculosis Pathogen

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A scientist by the name of Michael Niederweis described the first toxin from mycobacterium tuberculosis about six years ago. This toxin by the name of tuberculosis necrotizing toxin (TNT) is the founding member of the newly made class of previously unknown toxins found in more than 600 bacterial and fungal species.

Mycobacterium tuberculosis survives and grows inside the human host, and that is where it is released into the environment. There has been a lack of an identified toxin in M. Tuberculosis for over 132 years, which contrasts with nearly all other pathogenic bacteria whose toxins lead to illnesses or death. Mycobacterium tuberculosis contributes to 9 million infections per year and kills more than one million people.

How ESX Proteins From M. Tuberculosis Release Toxins

Researchers from the U.S National Science Foundation and the University of Alabama at Birmingham have explained how two small ESX proteins made by M. tuberculosis release the TNT to destroy host cells. The ESX proteins bring about TNT secretion through pore formation in the membrane that envelopes the bacteria.

EsxE and EsxF are WXG100 proteins with electron microscopy, mainly revealing pentameric structures with a central pore. Both WXG and GXW motif mutations do not affect dimerization. What these motifs do is abolish pore formation, membrane deformation and TNT secretion. 

This study reveals that WXG and GXW motifs are molecular switches controlling membrane interaction and membrane formation. The research also shows that the protein secretion mechanism in bacteria relies on pore formation by small WXG proteins.

Global Impact of Tuberculosis

TB symptoms include cough with sputum and blood, chest pains, weight loss, fever, and night sweats. Although TB affects mostly adults, all age groups are at risk. Over 95% of TB cases come from developing countries. Additionally, people infected with HIV are 18 times most likely to develop active TB. 

TB also significantly affects people with the impaired immune system and undernourished people. For example, in 2019 alone, there were 2.2 million new TB cases globally attributed to undernutrition. Other predisposing factors of TB infections include alcoholism and tobacco smoking. Alcoholism contributed to 0.72 million new TB cases in 2019, while smoking contributed to 0.70 million cases.

The disease is treatable and curable. Treatment is accompanied by giving support to the patients that help in treatment adherence. Although TB is difficult to diagnose in children, since 2000, WHO estimates 63 million lives have been saved through TB diagnosis and treatment.

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