Candidate transmission survival genome of <i>Mycobacterium tuberculosis</i>
Abstract
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (18)
Saurabh Mishra
Department of Microbiology and Immunology, Weill Cornell Medicine
Prabhat Ranjan Singh
Department of Microbiology and Immunology, Weill Cornell Medicine
Xiaoyi Hu
The Fluid Dynamics of Disease Transmission Laboratory, Fluids and Health Network, Department of Mechanical Engineering, Massachusetts Institute of Technology
Landys Lopez-Quezada
Department of Microbiology and Immunology, Weill Cornell Medicine
Adrian Jinich
Department of Chemistry and Biochemistry, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego
Robin Jahn
The Fluid Dynamics of Disease Transmission Laboratory, Fluids and Health Network, Department of Mechanical Engineering, Massachusetts Institute of Technology
Luc Geurts
The Fluid Dynamics of Disease Transmission Laboratory, Fluids and Health Network, Department of Mechanical Engineering, Massachusetts Institute of Technology
Naijian Shen
The Fluid Dynamics of Disease Transmission Laboratory, Fluids and Health Network, Department of Mechanical Engineering, Massachusetts Institute of Technology
Michael A. DeJesus
Laboratory of Host-Pathogen Biology, Rockefeller University
Travis Hartman
Department of Medicine, Weill Cornell Medicine
Kyu Rhee
Department of Medicine, Weill Cornell Medicine
Matthew Zimmerman
Center for Discovery and Innovation, Hackensack Meridian Health
Véronique Dartois
Center for Discovery and Innovation, Hackensack Meridian Health
Richard M. Jones
Department of Microbiology, University of Washington
Xiuju Jiang
Department of Microbiology and Immunology, Weill Cornell Medicine
Ricardo Almada-Monter
Department of Chemistry and Biochemistry, University of California San Diego
Lydia Bourouiba
The Fluid Dynamics of Disease Transmission Laboratory, Fluids and Health Network, Department of Mechanical Engineering, Massachusetts Institute of Technology
Carl Nathan
Department of Microbiology and Immunology, Weill Cornell Medicine