A $5.8 million grant led by Adrie Steyn, Ph.D., of the University of Alabama at Birmingham and the Africa Health Research Institute, or AHRI, in Durban, South Africa, will provide user-requested infected human lung tissue and analytical services to tuberculosis researchers worldwide.

It has been uncertain how Mycobacterium tuberculosis deflects the immune response in humans, though evidence has pointed to host immunometabolism — the intrinsic link between metabolism in immune cells and their immune function. The pathogen M. tuberculosis is known to disrupt a metabolic pathway called glycolysis in infected myeloid cells, which include macrophages, through an unclear mechanism. 

Gross anatomy reveals three-dimensional shapes of pathology at a large scale. Histology, in contrast, reveals the microscopic anatomy of biological structures. But that magnification comes at a cost — histology shows only two-dimensional shapes because it studies small, flat slices of stained tissue.

Lei Zhang, Ph.D., and Michael Niederweis, Ph.D., of the University of Alabama at Birmingham have made what they call “a major step” in understanding how Mycobacterium tuberculosis acquires iron from its human host — a process essential for the pathogenesis of this bacterium. Tuberculosis kills more than 1 million people each year, but without iron, M. tuberculosis cannot grow.

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. 

For 70 years, clinicians thought they knew the shape of tuberculosis granulomas in the lungs of patients. Histology — the study of microscopic structures in thin slices of lung tissue in the 1940s and 1950s — showed round features, and researchers intuitively assumed that meant the granulomas were spherical or ovoid. 

Six years ago, Michael Niederweis, Ph.D., described the first toxin ever found for the deadly pathogen Mycobacterium tuberculosis. This toxin, tuberculosis necrotizing toxin, or TNT, became the founding member of a novel class of previously unrecognized toxins present in more than 600 bacterial and fungal species, as determined by protein sequence similarity. The toxin is released as M. tuberculosis bacteria survive and grow inside their human macrophage host, killing the macrophage and allowing the escape and spread of the bacteria.

A new culprit — hydrogen sulfide — has been found for the deadly infectious disease tuberculosis. Hydrogen sulfide gas is known for its rotten egg smell, yet it has normal physiological roles in the human body to communicate among cells.

Using freshly resected lung tissue from 21 patients and two distinct mouse models, tuberculosis researchers at the University of Alabama at Birmingham and the Africa Health Research Institute, or AHRI, have identified a protein that plays an essential role in host defense against this deadly disease.

The bacteria that cause the devastating disease tuberculosis have the ability to escape destruction and grow after they are engulfed by lung macrophages, the immune cells that are supposed to destroy pathogens. Now researchers at the University of Alabama at Birmingham have described key biochemical steps between the bacteria Mycobacterium tuberculosis and the macrophage responsible for that ability.