Tuberculosis (TB) has haunted humanity for centuries, claiming over a million lives annually and remaining the leading cause of death from a single infectious pathogen worldwide. Its stubborn persistence challenges scientists and medical professionals alike, underscoring the urgent need for deeper insights into its modes of transmission. Traditional approaches, while improving treatment outcomes, have yet to fully unravel the complexities of how TB spreads through the air, particularly at the microscopic droplet level. Breaking new ground, researchers from the Hackensack Meridian Center for Discovery and Innovation (CDI), in collaboration with Massachusetts Institute of Technology (MIT) and Weill Cornell Medicine, have crafted a pioneering experimental platform designed to mimic the exact dynamics of tuberculosis transmission. This innovative system promises to revolutionize the understanding of aerogenic TB spread with unprecedented fidelity and precision.
At the forefront of this initiative is Dr. Martin Gengenbacher, Ph.D., an associate member of the CDI faculty whose collaborative team published their seminal findings in the renowned journal mBio. Their work details the development of the Transmission Simulation System (TSS), an advanced apparatus that replicates the human cough—a critical factor in airborne disease transmission—with remarkable accuracy. Unlike conventional models that often subjected test animals to nebulized bacterial clouds lacking physiological realism, the TSS captures the intricate physics of cough-generated aerosols, providing an authentic simulation of the droplets’ size distribution, concentration, and trajectory. This breakthrough not only enhances experimental control but also enables the detailed study of Mycobacterium tuberculosis as it travels suspended in aerosolized particles, capturing the crucial airborne phase that has eluded precise scrutiny until now.
Tuberculosis spreads primarily through aerosol droplets expelled during coughing episodes by infected individuals. Historically, research focused on exposing animals to dense nebulized bacteria, a method that failed to reproduce the complex aerosol environment generated by natural coughs. This gap in experimental models posed a significant barrier to dissecting the factors influencing transmission efficiency, droplet survival, and the infectious dose required to initiate lung infection. The TSS now overcomes these limitations by employing tailored hardware and software to generate cough aerosols that mirror the particle size distribution and concentration found in human patients with active TB. This is achieved through meticulous calibration of airflow dynamics and droplet propulsion forces, mimicking the biomechanics of human respiratory expulsions.
One of the system’s most significant innovations lies in its “nose-only” pickup simulation. This design feature replicates the natural inhalation route of TB droplets, enabling the downstream capture and analysis of inhaled aerosols by experimental animal models. By focusing exposure solely to the respiratory tract, the TSS avoids confounding variables often introduced by whole-body exposure chambers, thus increasing the reliability and physiological relevance of infection outcomes. This precision allows researchers to unravel pathogen-host interaction stages with greater clarity, observing how tuberculosis bacteria survive, persist, or are neutralized within the airways during the earliest moments post-inhalation.
The TSS is not only a marvel of bioengineering but also a game-changer for infection biology. Dr. Gengenbacher emphasizes that this laboratory-controlled mimicry of TB transmission opens new avenues for studying the vulnerabilities of Mycobacterium tuberculosis within its airborne phase—critical knowledge that could inform targeted strategies aimed at disrupting transmission chains. Understanding how aerosolized bacteria withstand environmental stressors and evade immune defenses in transit has long been an elusive yet crucial piece of the epidemiological puzzle. The precise quantification of aerosol characteristics and infection dynamics achievable with the TSS will likely accelerate the identification of novel molecular targets and therapeutic interventions.
Moreover, the potential of the TSS transcends tuberculosis alone. The platform’s capacity to replicate the mechanics of airborne contagion offers a versatile template for interrogating other pathogens transmitted via respiratory droplets or aerosols, such as influenza, SARS-CoV-2, or respiratory syncytial virus. David Perlin, Ph.D., CDI Chief Scientific Officer, highlights this potential, envisioning future deployment of the TSS or similarly engineered systems in the fight against a broad spectrum of airborne infectious diseases. This capacity for translational impact underscores the system’s significance not only as a research tool but as a cornerstone for global public health preparedness.
From a technical perspective, the TSS integrates sophisticated aerosol generators, real-time particle sensors, and exposure chambers that preserve the physical and biological integrity of expelled droplets. Its cough simulation incorporates programmable parameters that replicate the temporal force profile of a human cough, including peak airflow velocity and droplet emission patterns. This meticulous approach addresses previous experimental shortcomings where aerosol clouds lacked temporal and spatial fidelity, potentially skewing pathogen dose estimates and transmission risk assessments.
The research was funded by a Program Project Grant from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), highlighting the strategic emphasis placed on combating TB. This backing underlines the public health importance of developing precise models for infection and transmission and reflects confidence in the TSS’s potential to drive breakthroughs in vaccine development and novel therapeutic strategies. Indeed, the enhanced precision of this system can facilitate rigorous preclinical testing of new drugs and vaccines by providing an environment that closely replicates human transmission conditions.
As TB continues to pose a formidable challenge, especially in regions burdened by multidrug-resistant strains, tools such as the Transmission Simulation System offer a beacon of hope. By enabling scientists to systematically dissect the aerogenic phase of TB transmission with unprecedented control, this system could alter the trajectory of infectious disease research. It empowers researchers not only to quantify airborne pathogen loads but to understand the microenvironments that support bacterial survival and infectivity.
Dr. Gengenbacher and his team express optimism that continued collaborative efforts with MIT and Weill Cornell Medicine, bolstered by sustained support from federal funding agencies, will deepen understanding and accelerate the development of interventions capable of interrupting TB’s transmission pathway. Their work exemplifies how sophisticated experimental designs that simulate real-world biological phenomena can bridge the gap between laboratory research and clinical application, ultimately aiming to eliminate tuberculosis as a global killer.
In conclusion, the Transmission Simulation System marks a pivotal advancement in infectious disease research. By precisely emulating human respiratory emissions and modeling tuberculosis transmission under controlled laboratory conditions, this platform stands to unlock critical insights into pathogen dispersal, persistence, and infection initiation. It lays the groundwork for innovative therapeutics and vaccines that target the airborne transmission route—a domain previously shrouded by technical limitations. The implications of these advancements reach far beyond TB, promising to transform the study and control of airborne infectious diseases worldwide.
Subject of Research: Animals
Article Title: Experimental system enables studies of Mycobacterium tuberculosis during aerogenic transmission
News Publication Date: 25-Aug-2025
Web References:
- https://hmh-cdi.org/en
- https://www.mit.edu/
- https://weill.cornell.edu/
- https://journals.asm.org/doi/10.1128/mbio.00958-25
- https://asm.org/
- https://www.niaid.nih.gov/
- https://www.nih.gov/
References:
Gengenbacher M, et al. Experimental system enables studies of Mycobacterium tuberculosis during aerogenic transmission. mBio. 2025; DOI:10.1128/mbio.00958-25.
Image Credits: Hackensack Meridian Health
Keywords: Tuberculosis, Respiratory disorders, Diseases and disorders
