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Papers of the Week

Papers: 7 Mar 2020 - 13 Mar 2020

Animal Studies

2020 Mar 02


Mycobacterium tuberculosis Sulfolipid-1 Activates Nociceptive Neurons and Induces Cough.


Ruhl CR, Pasko BL, Khan HS, Kindt LM, Stamm CE, Franco LH, Hsia CC, Zhou M, Davis CR, Qin T, Gautron L, Burton MD, Mejia GL, Naik DK, Dussor G, Price TJ, Shiloh MU
Cell. 2020 Mar 02.
PMID: 32142653.


Pulmonary tuberculosis, a disease caused by Mycobacterium tuberculosis (Mtb), manifests with a persistent cough as both a primary symptom and mechanism of transmission. The cough reflex can be triggered by nociceptive neurons innervating the lungs, and some bacteria produce neuron-targeting molecules. However, how pulmonary Mtb infection causes cough remains undefined, and whether Mtb produces a neuron-activating, cough-inducing molecule is unknown. Here, we show that an Mtb organic extract activates nociceptive neurons in vitro and identify the Mtb glycolipid sulfolipid-1 (SL-1) as the nociceptive molecule. Mtb organic extracts from mutants lacking SL-1 synthesis cannot activate neurons in vitro or induce cough in a guinea pig model. Finally, Mtb-infected guinea pigs cough in a manner dependent on SL-1 synthesis. Thus, we demonstrate a heretofore unknown molecular mechanism for cough induction by a virulent human pathogen via its production of a complex lipid.