Protein Found to Protect Against Mycobacterium tuberculosis
The researchers discovered that the protein is responsible for immune response and destruction of the bacteria.
Researchers from UT Southwestern Medical Center recently found that a protein vital to the elimination of viruses in the body, also plays a role in the elimination of Mycobacterium tuberculosis (Mtb). The team, led by Michael Shiloh, MD, PhD, assistant professor at UT Southwestern Medical Center, and Beth Levine, MD, professor of internal medicine and microbiology, and director of UT Southwestern Medical Center’s Center for Autophagy Research, recently published their findings in Cell Host & Microbe.
Previously, researchers in Dr. Levine's lab had identified a protein, dubbed Smurf1, (not to be confused with the blue humanoids living in mushroom-shaped houses), that is imperative to viral elimination and "cleaning up" damaged mitochondria within cells through a physiological process called autophagy. Autophagy is responsible for a number of processes, including “eliminating pathogens such as viruses, parasites, and bacteria that get inside the cell.” For their study, the researchers wanted to analyze the effects of Smurf1 and its function in the process of eliminating bacteria, specifically, Mtb.
According to a press release on the study, "During antibacterial autophagy, the bacteria get tagged with the protein ubiquitin, marking them for destruction by an organelle called the lysosome. The role of Smurf1—one of hundreds of E3 ubiquitin ligases in mammals—was unknown in this process."
The researchers used a mouse model to learn more about the role of Smurf1. After studying the macrophages from mice that were lacking Smurf1, the researchers discovered that these mice "were unable to attach the death-tagging protein ubiquitin to intracellular bacteria, resulting in a failure of the autophagy pathway and runaway growth of the bacteria inside the cells." In addition, those mice without the Smurf1 protein that were infected with Mtb had, "higher bacterial loads, increased lung inflammation, and accelerated mortality compared to mice with normal Smurf1 activity."
The researchers were also able to determine that a Smurf1 gene exists that "controls Mtb growth in human macrophages," and that the Smurf1 protein "was found in association with bacteria in the lungs of patients with tuberculosis (TB) infections."
Dr. Shiloh commented on the results of the team’s findings, stating, “Even though humans mount a defense against Mtb that can contain its growth, in general that defense is insufficient to kill the bacteria. Finding ways to harness or enhance the autophagy pathway and Smurf1 could lead to new strategies to kill intracellular bacteria like those that cause TB.”
According to a press release, this new research may “lead to the development of immunity-based therapies to treat TB…by strengthening this immune pathway.”
Finding new ways to combat TB is particularly important as increasing rates of antibiotic resistance have caused the global TB epidemic to reach staggering proportions. According to the Centers for Disease Control and Prevention (CDC), approximately one-third of the human population is currently infected with TB. In addition, death rates are particularly high; in 2015 roughly 1.8 million deaths around the world were attributed to TB, with the disease being the “leading killer of people who are HIV-infected.” The CDC also reports that the economic toll caused by drug-resistant TB is extremely costly, with direct treatment costs for a single individual ranging between $18,000 and $494,000.