Mycobacterium tuberculosis Sulfolipid-1 Activates Nociceptive Neurons and Induces Cough

Cell
Cody R RuhlMichael U Shiloh

Abstract

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.

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Citations

Jan 27, 2021·Annual Review of Pathology·Rachel L KinsellaChristina L Stallings
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Aug 25, 2021·Proceedings of the National Academy of Sciences of the United States of America·Juhyeon LimHyungjin Eoh

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Methods Mentioned

BETA
biopsies
NMR
Confocal microscopy

Key Resources (RRID) Mentioned

CVCL_4Y33

Software Mentioned

MetaMorph
Volocity
MetaFluor Flourescence Ratio imaging
Buxco FinePointe
ImageJ
PeakView ( SCIEX )

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