Mycobacteria are a group of bacteria known to cause tuberculosis or leprosy, but not every bacterium in the genus is associated with these diseases.
A study completed at the University of Notre Dame in the laboratory of Jeff Schorey, the George B. Craig Jr. Professor of Biological Sciences, and published in PLOS Pathogens showed for the first time how RNA sensors drive a response in T-cells in one of the associated diseases, Mycobacterium avium Complex (MAC). The T-cells are crucial in driving the body’s immune response and fending off the disease.
The disease can damage the lungs and causes fever, chills, and various other symptoms depending on the site of the infection. Once seen primarily in patients with HIV infections, the disease has become more prevalent around the world, particularly among those with COPD, cystic fibrosis, and for reasons still unknown, in older, lean-bodied Caucasian and Asian women—and scientists are trying to find out why.
“It’s different from TB in that there’s not the person-to-person contact, and patients get it from an environmental source,” Schorey said, adding that the bacteria are frequently found in warm, moist environments like soil or in shower heads. MAC is difficult to treat, typically requiring a year to two years of drug treatment with a cure rate of only 50 percent. Patients are therefore left with managing a chronic infection so it does not cause more lung damage.
According to the study, the Mycobacterium avium (M. avium) release some of their RNA through the course of the infection. The M. avium, as well as the released RNA, are found in macrophages, which are large white blood cells. The bacterium’s RNA inside the infected macrophage induces its host cell to express an adhesion protein molecule that helps the T-cells stick to the infected cells. This promotes the killing of the M. avium within the macrophage.
“This is a host response protective mechanism, and we think that this is an important mechanism for controlling the infection,” said Schorey, who is affiliated with the Eck Institute for Global Health and the Boler-Parseghian Center for Rare and Neglected Diseases. “Most people don’t come down with the disease when they come into contact with Mycobacterium avium; it’s an opportunistic pathogen.”
This study, which took place in vitro and verified in mouse models, complements a drug development collaboration with Marvin Miller, professor emeritus in the Department of Chemistry and Biochemistry, and biopharmaceutical companies Hsiri Therapeutics and Shionogi & Co. The goal of this collaboration is the development of new antibiotics for treatment of MAC and other mycobacterial diseases.
“Treatment-wise we’re really far behind tuberculosis,” he said. “We don’t know a lot about the pathogen, and far fewer studies have been done, so our understanding of what makes it pathogenic in certain individuals is much less understood.”
In addition to Schorey, other researchers include Yong Cheng, research assistant professor in the Boler-Parseghian Center for Rare and Neglected Diseases and undergraduate students Nicholas J. Kiene, Alexandra Tatarian, and Emily F. Eix.
Funds for this work were provided by a grant from the National Institute of Allergy and Infectious Diseases.