# Mechanisms of cough in Mycobacterium tuberculosis transmission

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $707,736

## Abstract

Project Abstract
The success of any bacterial pathogen ultimately depends on its ability to multiply and transmit to new hosts.
Mycobacterium tuberculosis (Mtb), the causative agent of the human disease tuberculosis and one of the most
successful pathogens in human history, likely also employs sophisticated means to spread from one person to
the next, including mediating caseation, tissue destruction, and airborne transmission. Yet, despite the toll Mtb
has taken on world health, the molecular mechanisms responsible for Mtb transmission remain elusive. A
major symptom of active tuberculosis is cough, and cough is a major mechanism of transmission. Although
cough is a major route of aerosolization and transmission of Mtb, very little is known about the factors that
produce cough during infection. Furthermore, epidemiologic studies have demonstrated that Mtb strains
representing specific lineages are more prevalent in humans but whether differences in prevalence are due to
differences in bacterial transmissibility and associated factors such as cough induction and aerosolization of
bacteria is unknown. Thus, there is an urgent need to better characterize the transmission dynamics of Mtb
and the relationship of cough to transmission. Because nociceptive neurons mediate cough, and some bacteria
including mycobacteria secrete complex molecules targeting neurons, we hypothesized that Mtb produces
molecules to trigger nociceptive neurons to activate the cough response, thereby facilitating transmission. We
discovered and characterized the activity of one such molecule, sulfolipid-1, and recently identified a second
molecule produced by virulent mycobacteria. In the proposed research we will (1) Identify and study the
sulfolid-1 receptor in neurons and experimental animals, (2) Characterize the activity of the second nociceptive
molecule in neurons and experimental animals, and determine how its activity combines with that of sulfolipid-1
(3) Develop and use a sophisticated Mtb transmission system to measure transmission, cough and aerosolized
particles safely and quantitatively and use the system to compare the transmissibility of a variety of Mtb
mutants lacking cough-inducing molecules. The proposed work is expected to identify novel factors associated
with nociceptive neuron activation, cough and mycobacterial transmission.

## Key facts

- **NIH application ID:** 10185506
- **Project number:** 1R01AI158688-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** MICHAEL SHILOH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $707,736
- **Award type:** 1
- **Project period:** 2021-03-08 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10185506

## Citation

> US National Institutes of Health, RePORTER application 10185506, Mechanisms of cough in Mycobacterium tuberculosis transmission (1R01AI158688-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10185506. Licensed CC0.

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