Experimental system enables studies of Mycobacterium tuberculosis during aerogenic transmission
Name
nuritdinov-et-al-2025-experimental-system-enables-studies-of-mycobacterium-tuberculosis-during-aerogenic-transmission.pdf
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Published version
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861.54 KB
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Author(s)
Nuritdinov, Frank
Woo, Joshua
Schmidt, Markus J
Odjourian, Narineh M
Cristaldo, Melissa
Dougher, Maureen
Antilus-Sainte, Rosleine
Heldt, Thomas
Rhee, Kyu
Bourouiba, Lydia
Date Issued
August 25, 2025
Journal
mBio
Publisher
American Society for Microbiology
Citation
Nuritdinov F, Woo J, Schmidt MJ, Odjourian NM, Cristaldo M, Dougher M, Antilus-Sainte R, Heldt T, Rhee K, Bourouiba L, Gengenbacher M. 2025. Experimental system enables studies of Mycobacterium tuberculosis during aerogenic transmission. mBio 16:e00958-25.
Version
Final published version
Abstract
Tuberculosis, a persistent public health challenge worldwide, is transmitted when exhaled Mycobacterium tuberculosis (Mtb) particles expelled from an infected individual are inhaled by a susceptible person. To study the adaptation of Mtb during transition between hosts, we developed a transmission simulation system (TSS) that combines controlled pathogen aerosolization and measurement of bioaerosol particle characteristics with in-flight sampling of Mtb and infection of mice by nose-only exposure. Using scattered-light spectrometry, we demonstrated that Mtb aerosol concentrations generated by the TSS better represented human cough than the aerosol concentrations produced by a full-body inhalation exposure system commonly used for Mtb infection of mice. Additionally, the TSS deposited clinically relevant low doses of Mtb into murine lungs with greater precision than the full-body inhalation exposure systems. The TSS revealed a linear correlation between Mtb inoculum concentration and pathogen deposition in murine lungs up to 200 colony-forming units. Higher inoculum concentrations led to a reduction in total particle number, which resulted in disproportionately lower pulmonary infection doses. Importantly, the particle size distributions of Mtb-laden aerosols produced by the TSS mirrored those of tuberculosis patient coughs, with 90% of culturable Mtb found in particles with aerodynamic diameters below 3.3 µm. In conclusion, the TSS represents a novel effective and precise translational platform enabling detailed biophysical and molecular studies of Mtb transmission.
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DOI of Published Version
https://doi.org/10.1128/mbio.00958-25
