Candidate transmission survival genome of Mycobacterium tuberculosis

• 成果类型: Article
• 署名作者: 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
• 署名单位: Cornell University; Weill Cornell Medicine; Massachusetts Institute of Technology (MIT); University of California System; University of California San Diego; University of California System; University of California San Diego; Rockefeller University; Cornell University; Weill Cornell Medicine; University of Washington; University of Washington Seattle; National Institute of Pharmaceutical Education & Research, S.A.S. Nagar (Mohali)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14318
• DOI: 10.1073/pnas.2425981122
• 发表日期: 2025-03-11
• 关键词: guinea-pigs; aerosols; neutrophils; expression; granulomas; infection; viscosity; proteins

摘要

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.