Experimental system enables studies of during aerogenic transmission.

Abstract:

Tuberculosis, a persistent public health challenge worldwide, is transmitted when exhaled (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.