Scientists at Harvard Medical School have shown for the first time that a common skin bacterium, Staphylococcus aureus can cause itch by acting directly on nerve cells. The findings, based on research in mice and in human cells, are published in journal Cell.
The research adds an important piece to the long-standing puzzle of itch and helps explain In such conditions, the equilibrium of microorganisms that keep our skin healthy is often thrown off balance, allowing S. aureus to flourish, the researchers said. Up until now, the itch that occurs with eczema and atopic dermatitis was believed to arise from the accompanying inflammation of the skin. But the new findings show that S. aureus single-handedly causes itch by instigating a molecular chain reaction that culminates in the urge to scratch.
“We’ve identified an entirely novel mechanism behind itch :the bacterium Staph aureus, which is found on almost every patient with the chronic condition atopic dermatitis. We show that itch can be caused by the microbe itself,” said Isaac Chiu, senior author, associate professor of immunology in the Blavatnik Institute at HMS
The study experiments showed that S. aureus releases a chemical that activates a protein on the nerve fibers that transmit signals from the skin to the brain.
Treating animals with an FDA-approved anti-clotting medicine successfully blocked the activation of the protein to interrupt this key step in the itch-scratch cycle.
The treatment relieved symptoms and minimized skin damage.
The findings can inform the design of oral medicines and topical creams to treat persistent itch that occurs with various conditions linked to an imbalance in the skin microbiome, such as atopic dermatitis, prurigo nodularis, and psoriasis.
The repeated scratching that is a hallmark of these conditions can cause skin damage and amplify inflammation.
“Itch can be quite debilitating in patients who suffer from chronic skin conditions. Many of these patients carry on their skin the very microbe we’ve now shown for the first time can induce itch,” said study first author Liwen Deng, a postdoctoral research fellow in the Chiu Lab.
Researchers exposed the skin of mice to S. aureus.
The animals developed intensifying itch over several days, and the repeated scratching caused worsening skin damage that spread beyond the original site of exposure.
Moreover, mice exposed to S. aureus became hypersensitive to innocuous stimuli that would not typically cause itch.
The exposed mice were more likely than unexposed mice to develop abnormal itching in response to a light touch.
The analyses showed that V8 triggers itch by activating a protein called PAR1, which is found on skin neurons that originate in the spinal cord and carry various signals -;touch, heat, pain, itch -; from the skin to the brain. Normally, PAR1 lies dormant but upon contact with certain enzymes, including V8, it gets activated. The research showed that V8 snips one end of the PAR1 protein and awakens it.
Experiments in mice showed that once activated, PAR1 initiates a signal that the brain eventually perceives as itch.
When researchers repeated the experiments in lab dishes containing human neurons, they also responded to V8, said the study.