Humanized skin model answers questions about transient carriers of MRSA

By Sally Robertson, B.Sc.Oct 30 2019Reviewed by Kate Anderton, B.Sc. (Editor)

Researchers at the Karolinska Institutet have made an important discovery that may explain why some people are only transient carriers of the superbug MRSA (methicillin-resistant Staphylococcus aureus). The team found that immune cells called neutrophils may control the bacterial number of MRSA present on the skin by killing the bacteria before they get a chance to invade and cause infection.

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Staph infections can be dangerous

The bacterium Staphylococcus aureus commonly colonizes human skin and mucosa. It most often causes skin infections but can lead to more severe conditions including sepsis, pneumonia and toxic shock syndrome, particularly among patients who have a compromised immune system. Staph infections usually resolve independently, but in some cases, they require treatment with antibiotics.

MRSA is a strain of the bacterium that has become resistant to antibiotics. The superbug is considered one of the main antibiotic-resistant threats in the United States, with the Centers for Disease Control and Prevention estimating that it kills more than 11,000 deaths per year.

MRSA is quickly becoming a global health concern, causing infections that range from painful skin sores through to illnesses such as pneumonia.

MRSA carriers

Many people are exposed to MRSA, but not everybody who is exposed becomes infected. In some individuals, the bacterium lives harmlessly on the skin or inside the nose, without causing any signs of infections.

These individuals (who are colonized with the bacteria but who do not become infected) are referred to as MRSA carriers.

On average, 30% of people are Staph carriers and an average of 1 to 5% are MRSA carriers. Although MRSA carriers may never become infected themselves, they can spread the bacteria to individuals who are more susceptible to infection.

Transient carriers of MRSA

Some individuals are transient carriers of MRSA, meaning the bacteria are carried and then spread through transient contamination without colonization persisting. This transient contamination is generally gone within 12 to 24 hours.

Now, Keira Melican, from the Department of Neuroscience, Karolinska Institutet and colleagues may have found an explanation for why some people are only transient carriers of MRSA.

The team developed a “humanized” mouse model, where human skin is grafted onto the skin of mice. This enabled the researchers to explore the human tissue immune response in vivo.

As reported in the journal Cell Reports, the researchers found that once they had colonized the human skin with MRSA, neutrophils were recruited to the area where they killed the antibiotic-resistant bug.

Human skin is more dynamic than previously thought

The study also demonstrated how dynamic human skin is. Previously, the outer layers of skin had been thought of as dry, “dead” and therefore an environment that would be difficult for microbes to colonize.

However, a growing body of evidence suggests that this is not the case.

The skin is an incredibly dynamic biological environment where immune cells and microbes stand-off against one another to maintain some kind of equilibrium, a fraught peace. Breaks in these equilibria typically lead to bad outcomes for humans, and understanding how this process works on the skin could have an impact on how we prevent and treat skin infection in the future."

Keira Melican, Department of Neuroscience, Karolinska Institutet

Gaining a better understanding of human tissue response

Staphylococcus aureus is a common bacterium capable of causing serious infections that are increasingly becoming resistant to antibiotic treatment. Understanding the human immune response in skin tissue is therefore critical to understanding how to control the spread of resistant bacteria.

One problem with using animals as models of human disease is that some aspects of their biology are fundamentally different. The authors of the current study say that by incorporating human elements into the models they use, they can get a clearer picture of human biology.

"We hope that our humanized skin model will help make sure that our results are relevant to humans, and not just mice," concludes Melican.