Understanding and Stopping TB Cough Simulator Brings New Precision to Tuberculosis Transmission Research

Tuberculosis remains the world’s deadliest infectious disease, but a breakthrough system now simulates the human cough with unprecedented accuracy. A Transmission Simulation System promises to transform how scientists study airborne spread and could pave the way for new therapies and vaccines.

Tuberculosis has been a scourge upon humanity throughout history. In killing more than a million each year worldwide, it remains the leading cause of death from a single infectious pathogen.

While treatments have evolved and improved over time in active TB infection, understanding its spread down to droplet level remains elusive. But as with any infectious disease, a detailed understanding of the microbiology remains the key to global efforts in public health toward control, and eventual eradication.

To that end, the research faculty at Hackensack Meridian Center for Discovery and Innovation (CDI), in collaboration with teams at the Massachusetts Institute of Technology (MIT) and Weill Cornell Medicine, have developed a new experimental system called Transmission Simulation System (TSS) that replicates the airborne transmission of TB–by simulating the human cough–with unparalleled realism and never-before-seen precision.

Led by Martin Gengenbacher, Ph.D., associate member of the CDI faculty, the collaborative team published their findings in a paper entitled, "Experimental system enables studies of Mycobacterium tuberculosis during aerogenic transmission," in medical journal mBio, a publication by the American Society of Microbiology.

The study was funded via Program Project Grant bestowed by the National Institute of Allergy and Infectious Diseases (NIAID), an entity under the National Institutes of Health (NIH).

With his writing team, lead author Dr. Gengenbacher suggests the TSS could revolutionize the development of new therapies and vaccines aimed at stopping the spread of the world’s deadliest infectious disease.

“Previous lab models relied on exposing animals to a dense, uncontrolled "fog" of bacteria via nebulizer to study TB transmission,” said Dr. Gengenbacher. “While practical, this was an imprecise method that didn’t sufficiently mirror real-world transmission.”

Dr. Gengenbacher said the system’s major breakthrough is its ability to mimic the key characteristics of a human cough and simulate the propulsion of aerosolized, infected droplets. The TSS also employs a “nose-only” pickup simulation to complete the transmission process. creating more consistent observations.

"This system allows us to accurately model the entire journey of tuberculosis in a controlled laboratory setting," said Dr. Gengenbacher. “Its aerosol concentration is more realistic than older methods, and its particle size distribution mirrors that of patients having active TB. We can now begin to study the vulnerabilities of the bacterium while it's airborne and develop strategies to specifically interrupt this transmission pathway.”

The thrill of discovery lies not just in this new system’s implications for interception of TB transmission, but in the ability to envision its potential for future reach into studying the spread of many infectious diseases.

"Being able to reliably replicate the process of human-to-human transmission opens a new frontier for testing interventions," said CDI Chief Scientific Officer and Executive Vice President David Perlin, Ph.D. “By studying the innovations of Dr. Gengenbacher’s team, we might one day apply similar technology to better understand and control the spread of other air- and droplet-borne diseases.”

With a lifetime of TB research behind them as context, this moment of development and innovation is not lost on Dr. Gengenbacher or his team, now.

“I’m thrilled to continue working with my teammates at MIT and Cornell, with continued support from the NIAID and NIH,” he said. “Through enhanced prevention by way of interception, we can one day defeat this disease as a global killer.”

Original Article: Experimental system enables studies of Mycobacterium tuberculosis during aerogenic transmission; mBio; DOI:10.1128/mbio.00958-25

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