Year: 2026
Type: article
Abstract: ABSTRACT Tuberculosis (TB) spreads through the air, yet the physical conditions that permit effective airborne transmission remain poorly defined. Although early 20th-century guinea pig studies demonstrated efficient transmission of Mycobacterium tuberculosis (Mtb), this experimental paradigm has not been reestablished in modern high-containment facilities. Here, we show that airflow can impose constraints that suppress or permit biologically effective exposure between infected and susceptible hosts. Using a guinea pig model of animal-to-animal exposure, we combined transmission experiments with quantitative particle tracking and particle transport modeling to explain why some housing configurations fail to support effective exposure. Static environments and excessive unidirectional airflow prevented transmission, whereas controlled low-velocity airflow restored evidence of exposure, including tuberculin skin test conversion, antigen-specific immune responses, and pulmonary inflammation consistent with early infection. These findings identify airflow as a critical constraint on airborne TB transmission and establish a reproducible experimental framework for dissecting host, microbial, and environmental determinants of spread. IMPORTANCE Tuberculosis remains one of the leading causes of death from infectious disease worldwide, and its spread depends on airborne transmission of Mycobacterium tuberculosis . Yet surprisingly little is known about the physical conditions that determine when transmission actually occurs. Classic experiments in guinea pigs demonstrated airborne spread of tuberculosis, but these systems have been difficult to reproduce in modern high-containment laboratories. In this study, we show that airflow conditions can determine whether pathogen-containing aerosols persist long enough to expose a susceptible host. By identifying airflow as a key constraint on transmission and establishing an experimental system that functions under contemporary biosafety conditions, this work provides a platform to experimentally dissect how microbial, host, and environmental factors interact to shape tuberculosis spread.
Source: mSphere
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,500
Funders: National Science Foundation, National Aeronautics and Space Administration, Burroughs Wellcome Fund, Analog Devices, University of Texas Southwestern Medical Center, MathWorks, National Institutes of Health, National Science Foundation of Sri Lanka, National Institute of Allergy and Infectious Diseases
Awards: G1196024891, PIPP Phase II: Analysis and Prediction of Pandemic Expansion (APPEX), Transmission dynamics of Mycobacterium tuberculosis, G443064334, G527156614, G6510110367, G8583101034, G8845047691, Probing the particle size-viability relationship in bioaerosols through size-controlled measurements, Chemical composition-viability relationship of bioaerosols through spatial distribution and size-controlled measurements, Defining the antibody interface between Mycobacterium tuberculosis and host immunity, Mechanisms of cough in Mycobacterium tuberculosis transmission
OpenAlex ID: W7203688756