Mycobacterium tuberculosis Sulfolipid-1 Activates Nociceptive Neurons and Induces Cough.
Cell
; 181(2): 293-305.e11, 2020 04 16.
Article
em En
| MEDLINE
| ID: mdl-32142653
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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Base de dados:
MEDLINE
Assunto principal:
Nociceptores
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Glicolipídeos
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Tosse
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Fatores de Virulência
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article