Study Uncovers How Tuberculosis Agent Survives on Fatty Acids

Researchers at the University of Alabama at Birmingham (UAB) have discovered a key mechanism behind the survival instinct of tuberculosis. TB is the leading cause of death in the world from a single bacterial infection, and it kills 1.5 million people per year.

The researchers looked at how Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, survives on fatty acids and regulates its metabolism to persist in humans for extended periods. Understanding Mtb persistence paves the way for finding new drugs and better vaccines to fight TB’s drug-resistant latent state, the researchers said.

Mtb latency is a global problem that results in TB infection escaping detection and treatment, and which contributes to overall TB illness and death.

The UAB study found a regulatory protein called WhiB3 that allows Mtb to subsist on fatty acids and adjust its metabolism to cope with stresses during infection. The findings are published in PLoS Pathogens, a journal of the nonprofit Public Library of Science.

“Our goal was to understand or come up with mechanisms for how Mtb enters, maintains and emerges from a persistent state of infection,” said Adrie J.C. Steyn, PhD, assistant professor in UAB’s Department of Microbiology and lead author on the study. “We identified the master regulatory protein of virulence lipid production: WhiB3.”

In the study, the researchers worked with Mtb cells under biosafe laboratory conditions and found that WhiB3 regulation of lipids helped keep the body’s immune system in check. The UAB team also developed a radio-labeling technique that for the first time reveals lipid changes of Mtb while growing in cultured host cells. The findings shed light on how pathogens modify their physiology to adapt to stresses during the course of infection.

Steyn conducted the research in partnership with the UAB Center for Emerging Infections and Emergency Preparedness, the UAB Center for Free Radical Biology, the UAB Department of Biochemistry and Molecular Genetics and the University of Colorado Denver. The research team includes Amit Singh, PhD; David K. Crossman, PhD; Deborah Mai, Loni Guidry, Martin I. Voskuil, PhD and Matthew B. Renfrow, PhD. Funding came from the National Institutes of Health.