Methods: We used an in vitro neuronal activation bioassay to fractionate, identify and characterize Mtb cough-inducing molecules. We also measured cough in vivo in response to pure Mtb-derived cough molecules and during Mtb infection using a guinea pig model.
Results: We found that an acellular organic extract of Mtb triggers and activates nociceptive neurons in vitro with a neuronal response that is as robust as the response to capsaicin, an established nociceptive and cough-inducing molecule. Using analytical chemistry and our neuronal bioassay, we then isolated two molecules produced by Mtb that activate nociceptive neurons. Both the organic Mtb extract and purified molecules alone were sufficient to induce cough in a conscious guinea pig cough model. Finally guinea pigs infected with wild type Mtb cough much more frequently than guinea pigs infected with Mtb strains unable to produce nociceptive molecules.
Conclusion: We conclude that Mtb produces molecules that activate nociceptive neurons and induce cough. These findings have significant implications for our understanding of Mtb transmission.
H. Khan, None
C. E. Stamm, None
B. Pasko, None
L. Franco, None
M. U. Shiloh, None