Proceedings of the National Academy of Sciences of the United States of America · 2025
Candidate transmission survival genome of Mycobacterium tuberculosis.
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Mishra Saurabh, Singh Prabhat Ranjan, Hu Xiaoyi, Lopez-Quezada Landys, Jinich Adrian, Jahn Robin, Geurts Luc, Shen Naijian, DeJesus Michael A, Hartman Travis, Rhee Kyu, Zimmerman Matthew, Dartois Veronique, Jones Richard M, Jiang Xiuju, Almada-Monter Ricardo, Bourouiba Lydia, Nathan Carl
Аннотация
Mycobacterium tuberculosis (Mtb), a leading cause of death from infection, completes its life cycle entirely in humans except for transmission through the air. To begin to understand how Mtb survives aerosolization, we mimicked liquid and atmospheric conditions experienced by Mtb before and after exhalation using a model aerosol fluid (MAF) based on the water-soluble, lipidic, and cellular constituents of necrotic tuberculosis lesions. MAF induced drug tolerance in Mtb, remodeled its transcriptome, and protected Mtb from dying in microdroplets desiccating in air. Yet survival was not passive: Mtb appeared to rely on hundreds of genes to survive conditions associated with transmission. Essential genes subserving proteostasis offered most protection. A large number of conventionally nonessential genes appeared to contribute as well, including genes encoding proteins that resemble antidesiccants. The candidate transmission survival genome of Mtb may offer opportunities to reduce transmission of tuberculosis.