Common microbe found to be the culprit behind skin itch

In a groundbreaking discovery, Harvard Medical School (HMS) scientists have revealed that Staphylococcus aureus, a common skin bacterium, can directly cause itch by acting on nerve cells.

This new understanding, reported in the journal Cell, unravels a piece of the complex puzzle of itch and explains the persistent itching associated with skin conditions like eczema and atopic dermatitis.

Molecular chain reaction

These conditions often disrupt the skin’s microbial balance, leading to an overgrowth of S. aureus. Previously, it was believed that the accompanying skin inflammation was the primary cause of itch in these cases. However, this new research demonstrates that S. aureus alone can trigger itch through a specific molecular chain reaction, culminating 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 senior author Isaac Chiu, an associate professor of Immunology at the Blavatnik Institute at HMS.

Managing persistent itch 

The researchers found that S. aureus releases a chemical that activates a protein on nerve fibers that transmit signals from the skin to the brain. When mice were treated with an FDA-approved anti-clotting medicine that blocks the activation of this protein, there was a significant interruption in the itch-scratch cycle, providing symptom relief.

This discovery paves the way for the development of new oral and topical treatments to manage persistent itch in various conditions linked to skin microbiome imbalances, such as atopic dermatitis, prurigo nodularis, and psoriasis. The repetitive scratching characteristic of these conditions can lead to skin damage and heightened 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.

Focus of the study 

The researchers’ experiments involved exposing mice to S. aureus, leading to increasing itch intensity and worsening skin damage due to repetitive scratching. 

The mice also developed alloknesis, becoming hypersensitive to normally non-itch-inducing stimuli. This hyperactive response mirrors the condition in patients with chronic skin ailments characterized by persistent itching.

To identify the bacterial trigger, the team experimented with various modified strains of S. aureus, each lacking specific molecular components. They discovered that the bacterial enzyme protease V8 was solely responsible for initiating itch in the mice. Human skin samples from patients with atopic dermatitis also showed elevated levels of S. aureus and the V8 enzyme.

Critical insights 

The study demonstrates that V8 triggers itch by activating a protein called PAR1 on skin neurons, which are responsible for relaying various signals, including itch, from the skin to the brain. The experiments further revealed that, once activated, PAR1 initiates a signal that the brain perceives as itch. This response was also observed in human neurons in lab experiments.

Intriguingly, the researchers found that various immune cells and inflammatory chemicals, typically implicated in skin allergies and known to cause itch, did not drive it after bacterial exposure.

“When we started the study, it was unclear whether the itch was a result of inflammation or not,” Deng said. “We show that these things can be decoupled, that you don’t necessarily have to have inflammation for the microbe to cause itch, but that the itch exacerbates inflammation on the skin.”

Study implications 

Furthermore, the researchers explored the potential of using PAR1 blockers. Mice treated with these blockers experienced a rapid improvement, with a notable decrease in their urge to scratch and subsequent skin damage.

Overall, these findings highlight a novel mechanism for itch and offer potential pathways for the development of new treatments targeting the skin microbiome.

The research underlines the importance of further exploring the molecular interactions between skin microbes and the nervous system to advance our understanding and management of itch in various skin conditions.

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