# Project 3: Mechanisms of cough in M. tuberculosis transmission

> **NIH NIH P01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $517,405

## Abstract

Project Summary/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 or other factors predicted to impact transmission. The proposed 
work is expected to identify novel factors associated with nociceptive neuron activation, cough and 
mycobacterial transmission.

## Key facts

- **NIH application ID:** 10190651
- **Project number:** 1P01AI159402-01
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** MICHAEL SHILOH
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $517,405
- **Award type:** 1
- **Project period:** 2021-05-13 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190651

## Citation

> US National Institutes of Health, RePORTER application 10190651, Project 3: Mechanisms of cough in M. tuberculosis transmission (1P01AI159402-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10190651. Licensed CC0.

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