International Business Department           Liu Bojia           November 24, 2023

  Many people have had problems with itchy skin and in some cases the more they scratch the more itchy they get, causing breaks in the skin barrier and infections, and severe itchy skin can also be linked to eczema or atopic dermatitis. But why would an intact skin barrier suddenly become itchy? Some studies have suggested that it's caused by inflammation, a claim that may only explain part of the reason.

  According to the latest Cell study, researchers from Harvard Medical School have found that another cause of itchy skin is a common bacterium, Staphylococcus aureus. This bacterium is found in the nasal passages, hair and skin of humans and can cause infections when the immune system is low. Massive colonisation of Staphylococcus aureus leads to disruption of skin flora and activation of itch-related signalling pathways.

  At the beginning of the study, when the authors analysed some samples from patients with atopic dermatitis, they found that almost every patient had a lot of S. aureus on their skin, suggesting that this bacterium is involved in an unknown pathological process.

  To test their speculation, the study injected Staphylococcus aureus under the skin of experimental mice, and after a few days, the mice began to develop itchy, scratching behaviour, and in some cases, this led to skin lesions that allowed the infected area to spread.

  In addition to the normal itching, the infected areas of the mice were particularly sensitive to other stimuli, and even the slightest touch caused the mice to itch. The symptoms are similar to those of alloknesis in humans, in which patients typically experience chronic itching of the skin and itch in response to common stimuli.

  Surprisingly, the researchers did not detect inflammation in the mice's skin, including no changes in levels of interleukins or other inflammatory factors, which also suggests that inflammation is not necessary for itch to occur. The researchers noted that in the past it was thought that the link between bacteria and itch was indirect, with inflammation needed to mediate the middle ground, but in fact the bacteria themselves alone are sufficient to trigger itch.

  To confirm the mechanism by which Staphylococcus aureus causes itch, the study engineered a variety of modified strains of the bacterium, each of which lacks a specific type of enzyme that is released when the bacteria come into contact with the skin and is the prime suspect for causing itch.

  Of all the strains, one Staphylococcus aureus that lacked the protease V8 produced exceptional results, with all mice infected with this bacterium no longer developing itchy skin. Specifically, the V8 enzyme also doesn't work on its own; it needs to bind to PAR1 receptors in skin neurons to activate downstream itch-related signalling.

  PAR1 receptor is usually responsible for transmitting all kinds of complex skin signals, including touch, heat, pain and itch. In the absence of stimulation PAR1 is in a state of shutdown, so normally there is no abnormal sensation in the skin. Instead, the V8 enzyme binds to it and triggers the itch signal.

  The authors tried giving infected mice Vorapaxar, a drug used to prevent blood clots that blocks PAR1 receptors, and as a result the itchiness disappeared after a period of time. But more experiments are needed to confirm whether this approach is effective in humans.

  In addition to the mechanism of bacteria and itching, the team had an even more curious question: why does Staphylococcus aureus trigger itching? Many bacteria evolve to promote their growth and spread by triggering specific symptoms, such as Mycobacterium tuberculosis, which causes coughing and accelerates the infection of more hosts. The authors speculate that itching may allow S. aureus to hijack neurons to gain a survival advantage, or it may allow the animal to scratch its skin to increase the extent of the infection, thus allowing itself to spread farther.