Candidate transmission survival genome of Mycobacterium tuberculosis

Saurabh Mishra; Prabhat Ranjan Singh; Xiaoyi Hu; Landys Lopez-Quezada; Adrian Jinich; Robin Jahn; Luc Geurts; Naijian Shen; Michael A. DeJesus; Travis Hartman; Kyu Rhee; Matthew Zimmerman; Veronique Dartois; Richard M. Jones; Xiuju Jiang; Ricardo Almada-Monter; Lydia Bourouiba; Carl Nathan

doi:10.1073/pnas.2425981122

Candidate transmission survival genome of Mycobacterium tuberculosis

Saurabh Mishra
, Prabhat Ranjan Singh
, Xiaoyi Hu
, Landys Lopez-Quezada
, Adrian Jinich
, Robin Jahn
, Luc Geurts
, Naijian Shen
, Michael A. DeJesus
, Travis Hartman
, Kyu Rhee
, Matthew Zimmerman
, Veronique Dartois
, Richard M. Jones
, Xiuju Jiang
, Ricardo Almada-Monter
, Lydia Bourouiba
, Carl Nathan

Center for Discovery and Innovation

National Institute of Pharmaceutical Education and Research, Mohali
Cornell University
Massachusetts Institute of Technology
University of California at San Diego
Rockefeller University
University of Washington

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

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.

Original language	English
Article number	e2425981122
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	122
Issue number	10
DOIs	https://doi.org/10.1073/pnas.2425981122
State	Published - 11 Mar 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Mycobacterium
aerosol
biophysics
transmission
tuberculosis

Access to Document

10.1073/pnas.2425981122

Cite this

Mishra, S., Singh, P. R., Hu, X., Lopez-Quezada, L., Jinich, A., Jahn, R., Geurts, L., Shen, N., DeJesus, M. A., Hartman, T., Rhee, K., Zimmerman, M., Dartois, V., Jones, R. M., Jiang, X., Almada-Monter, R., Bourouiba, L., & Nathan, C. (2025). Candidate transmission survival genome of Mycobacterium tuberculosis. Proceedings of the National Academy of Sciences of the United States of America, 122(10), Article e2425981122. https://doi.org/10.1073/pnas.2425981122

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title = "Candidate transmission survival genome of Mycobacterium tuberculosis",

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.",

keywords = "Mycobacterium, aerosol, biophysics, transmission, tuberculosis",

author = "Saurabh Mishra and Singh, \{Prabhat Ranjan\} and Xiaoyi Hu and Landys Lopez-Quezada and Adrian Jinich and Robin Jahn and Luc Geurts and Naijian Shen and DeJesus, \{Michael A.\} and Travis Hartman and Kyu Rhee and Matthew Zimmerman and Veronique Dartois and Jones, \{Richard M.\} and Xiuju Jiang and Ricardo Almada-Monter and Lydia Bourouiba and Carl Nathan",

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doi = "10.1073/pnas.2425981122",

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Mishra, S, Singh, PR, Hu, X, Lopez-Quezada, L, Jinich, A, Jahn, R, Geurts, L, Shen, N, DeJesus, MA, Hartman, T, Rhee, K, Zimmerman, M , Dartois, V, Jones, RM, Jiang, X, Almada-Monter, R, Bourouiba, L & Nathan, C 2025, 'Candidate transmission survival genome of Mycobacterium tuberculosis', Proceedings of the National Academy of Sciences of the United States of America, vol. 122, no. 10, e2425981122. https://doi.org/10.1073/pnas.2425981122

TY - JOUR

T1 - Candidate transmission survival genome of Mycobacterium tuberculosis

AU - Mishra, Saurabh

AU - Singh, Prabhat Ranjan

AU - Hu, Xiaoyi

AU - Lopez-Quezada, Landys

AU - Jinich, Adrian

AU - Jahn, Robin

AU - Geurts, Luc

AU - Shen, Naijian

AU - DeJesus, Michael A.

AU - Hartman, Travis

AU - Rhee, Kyu

AU - Zimmerman, Matthew

AU - Dartois, Veronique

AU - Jones, Richard M.

AU - Jiang, Xiuju

AU - Almada-Monter, Ricardo

AU - Bourouiba, Lydia

AU - Nathan, Carl

PY - 2025/3/11

Y1 - 2025/3/11

N2 - 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.

AB - 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.

KW - Mycobacterium

KW - aerosol

KW - biophysics

KW - transmission

KW - tuberculosis

UR - https://www.scopus.com/pages/publications/86000500202

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DO - 10.1073/pnas.2425981122

M3 - Article

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AN - SCOPUS:86000500202

SN - 0027-8424

VL - 122

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 10

M1 - e2425981122

ER -

Candidate transmission survival genome of Mycobacterium tuberculosis

Abstract

UN SDGs

Keywords

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