Kansas recently confirmed one of the largest Tuberculosis outbreaks in U.S. history. This has prompted renewed focus on prevention efforts and public health preparedness. While the United States maintains low TB incidence rates globally, the country has experienced a significant increase in cases in the last few years.
Tuberculosis (TB) is one of the world’s oldest and most persistent infectious diseases, affecting billions every year. Caused by Mycobacterium tuberculosis (M. tuberculosis), TB primarily targets the lungs but can also impact other vital organs. It spreads through the air when an infected person coughs or sneezes.
While many people carry the bacteria without symptoms, about 5 percent of people develop active TB, which can be fatal without treatment. Recognizing symptoms like a persistent cough, fever, and fatigue is crucial, as untreated TB can have severe health consequences.
"The recent tuberculosis outbreak in Kansas is an unambiguous reminder of the challenges in our public health infrastructure,” explained J. Victor Garcia-Martinez, Ph.D., professor and Charles H. McCauley Endowed Chair in the UAB Department of Microbiology. “With 69 active TB cases and 90 latent cases reported since early 2024 by the Division of Public Health of the Kansas Department of Health and Environment, this outbreak, mostly taking place in Wyandotte County, Kansas, is one of the largest in recent U.S. history. While it is important to indicate that the general risk to the public remains low, the outbreak highlights the importance of testing, tracing, and treatment to prevent further spread. One of the most pressing issues is ensuring timely diagnosis and treatment, especially in high-risk settings.”
Andries Steyn, Ph.D., Michael Niederweis, Ph.D., and J. Victor Garcia, Ph.D., members of the Department of Microbiology, provide insight into groundbreaking research at UAB to further understand and combat tuberculosis.
Breakthroughs in TB
UAB researchers are making significant strides in TB science. In a recent breakthrough, the Steyn lab recently used high-resolution micro/nano computed tomography (µ/nCT) to map the 3D structure of human TB granulomas.
“This groundbreaking discovery challenges the long-held belief that granulomas are spherical, revealing them to be cylindrical,” Steyn said. “This new understanding offers fresh insights into granuloma formation and M. tuberculosis spread through the lungs.”
The Steyn lab is also exploring how micronutrients like vitamin B3 influence M. tuberculosis, how they alter host metabolism, and the role of hydrogen sulfide (H₂S) in infection outcomes. The lab’s use of multimodal spatial platforms and AI-driven analysis of digitized TB lesions is paving the way for next-generation diagnostics and vaccines.
“Our work in tuberculosis spans every stage from basic science to clinical science,” Steyn said. “Through strategic partnerships, we're helping drive innovation in TB research and advancing efforts to eliminate the disease worldwide.”
Similarly, the Niederweis lab has made history by being the first to visualize the outer membrane of M. tuberculosis using cryo-electron microscopy.
“This membrane plays a crucial role in the bacterium’s drug resistance and virulence,” Niederweis stated. “By identifying several novel outer membrane proteins the lab is uncovering new pathways for TB chemotherapy.”
Additionally, the Niederweis lab identified TNT as the first exotoxin of M. tuberculosis, which presents a new opportunity to explore host-targeted treatment strategies.
Targeting TB in new ways
UAB researchers are also exploring innovative approaches to TB treatment. The Steyn lab is advancing metallomics research to develop noninvasive imaging techniques for detecting TB-specific lesions. The team is also investigating host-directed therapies (HDTs), which aim to modulate the body’s immune response rather than targeting the bacteria directly.
“These efforts, alongside the development of a high-resolution digital atlas of the human TB lung being examined by AI-driven analysis, are providing critical insights for the next generation of TB vaccines,” Steyn said.
Meanwhile, the Niederweis Lab is exploring a different vulnerability in M. tuberculosis: its outer membrane proteins.
“These proteins are not only essential to the pathogen’s survival but also constitute accessible drug targets, unlike interior proteins shielded by the bacteria’s robust permeability barrier,” Niederweis said. The lab is investigating these proteins as a new path to novel drug targets to improve TB chemotherapy.
Another area of emphasis is the development an implementation of long-acting formulations for TB prevention and treatment being conducted in the Garcia lab.
“Long-acting (LA)drug formulations for tuberculosis treatment and prevention are crucial as they can significantly improve patient adherence by reducing the frequency of doses required and thus enhancing treatment outcomes,” Garcia explained. “These formulations also have the potential to simplify TB management, making it easier to control and prevent the spread of the disease. LA- formulation have the potential of serving as a 1-shot cure.”
Challenges in TB research and how UAB is preparing
Despite significant progress in diagnostics, treatments, and public health strategies, TB research faces substantial challenges. These hurdles are emerging across several key areas, including the detection of asymptomatic and latent infections, the development of rapid diagnostics for drug-resistant strains (particularly multi-drug-resistant [MDR] and extensively drug-resistant [XDR] TB), host-directed therapies (HDTs), and the complex issues of TB-HIV and TB-COVID-19 co-infection.
“UAB is addressing these challenges by recruiting and retaining world-class faculty specializing in TB research,” Steyn expressed. “The university is leading innovative research initiatives, fostering collaborations, and providing comprehensive training for the next generation of TB scientists.”
These efforts are crucial in advancing the science and strategies needed to address the evolving landscape of TB.