Mycobacterial Phenolic Glycolipid Triggers ATP-Mediated Neuronal P2X3 Signaling and Cough.

ABSTRACT: Cough drives respiratory pathogen transmission, yet how microbes directly engage host sensory neurons to trigger cough is largely unknown. We previously demonstrated that the Mycobacterium tuberculosis (Mtb) glycolipid sulfolipid-1 (SL-1) activates neurons and induces cough. Here, we reveal that phenolic glycolipid (PGL) produced by the hypertransmissible HN878 Mtb strain activates both mouse and human nociceptive neurons in vitro using calcium imaging and electrophysiology and is sufficient to induce cough using plethysmography. Combined with SL-1, PGL potently triggers neuronal activation. By synthesizing various PGL analogs, we show that neuroactivity is proportional to saccharide chain length and structure. Mechanistically, PGL stimulates rapid extracellular ATP release, which e

SUBMITTER: Naqvi KF 

PROVIDER: S-EPMC12248122 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature