S. aureus drives itch and scratch-induced skin damage through a V8 protease-PAR1 axis
Publication information:
Liwen Deng, Flavia Costa, Kimbria Blake, Samantha Choi, Arundhasa Chandrabalan, Muhammad Saad Yousuf, Stephanie Shiers, Daniel Dubreuil, Daniela Vega-Mendoza, Corinne Rolland, Celine Deraison, Tiphaine Voisin, Michelle Bagood, Lucia Wesemann, Abigail Frey, Joseph Palumbo, Brian Wainger, Richard Gallo, Juan-Manuel Leyva-Castillo, Nathalie Vergnolle, Theodore Price, Rithwik Ramachandran, Alexander Horswill, and Isaac Chiu. 2023. “S. Aureus Drives Itch and Scratch-Induced Skin Damage through a V8 Protease-PAR1 Axis”. Cell, 186, 24, Pp. 5375-5393.e25. doi:10.1016/j.cell.2023.10.019
Abstract
Itch is an unpleasant sensation that evokes a desire to scratch. The skin barrier is constantly exposed to microbes and their products. However, the role of microbes in itch generation is unknown. Here, we show that Staphylococcus aureus, a bacterial pathogen associated with itchy skin diseases, directly activates pruriceptor sensory neurons to drive itch. Epicutaneous S. aureus exposure causes robust itch and scratch-induced damage. By testing multiple isogenic bacterial mutants for virulence factors, we identify the S. aureus serine protease V8 as a critical mediator in evoking spontaneous itch and alloknesis. V8 cleaves proteinase-activated receptor 1 (PAR1) on mouse and human sensory neurons. Targeting PAR1 through genetic deficiency, small interfering RNA (siRNA) knockdown, or pharmacological blockade decreases itch and skin damage caused by V8 and S. aureus exposure. Thus, we identify a mechanism of action for a pruritogenic bacterial factor and demonstrate the potential of inhibiting V8-PAR1 signaling to treat itch.
Notes
- “S. aureus scratches an itch,” Jack Major and Shruti Naik. Cell. 2023; 186(24):5201-5202.
- National Public Radio (NPR): “What can trigger an itch? Scientists have found a new culprit.” All Things Considered. Nov. 22, 2023.
- BBC Science Focus Magazine: “Scientists finally work out what causes itching – and its grosser than you’d think,” Nov. 22, 2023.
- Boston Globe: “Harvard University researchers discover one of the origins of itch,” Nov 22, 2023.
- NBC News: “What causes the skin to itch? New research points to a previously unknown factor,” Nov. 22, 2023.
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