Inspiration

The skin is our largest organ. Unfortunately for one third of the population, their skin is affected by skin disease (Flohr and Hay 2021). This not only negatively influences their physical but for many also decreases their mental health (Schuster et al. 2020). Understanding the cause and mechanism of a disease is important to design an effective treatment plan, but also to improve self-awareness.

Naturally, the skin is covered by bacteria, which together with other species, like fungi, form the so-called skin microbiota. These bacteria are important for different aspects, for example to develop a healthy immune system and to retain a healthy skin barrier (Boxberger et al. 2021). However, if certain bacterial species colonize the skin or the ratio of normally harmless bacteria drastically changes it can result in various skin diseases.

The best known and most common skin disease in adolescents is acne vulgaris. The origin of the chronic inflammatory disease is a complex network between genetic and environmental factors (Moradi Tuchayi et al. 2015). The bacterial strain Cutibacterium acnes (C.acnes) is suspected to negatively impact the process of acne vulgaris progression. While for a long time it was believed that an increase in total C.acnes population of the skin causes the disease, nowadays studies show that dysbiosis, meaning an imbalance in ratio between the different C.acnes strains, is associated with the disease (Dréno et al. 2020) (add more ref).

IMAGE HERE ASK CAROLIN FIRST IF THIS IS OK TO USE, ITS FROM AN ARTICLE I THINK. WE CAN REMAKE IT AND THEN ADD IT MAYBE

Even so, it is known that acne is caused by multiple factors, the European guidelines for treating acne vulgaris include the use of broad-spectrum antibiotics (Nast et al. 2012; Patel and Bhatia 2021). Broad-spectrum antibiotic use cleanses the skin from nearly all bacteria, which may help in reducing the symptoms short-term, but changes the normal microbiome long-term and may result in antibiotic resistance of bacteria (Patel and Bhatia 2021).

Atopic dermatitis is another skin disease associated with microbiota dysbiosis. In atopic dermatitis, patients suffer from itching skin lesions, which can lead to cutaneous infections. The formation of the disease is, like in acne vulgaris, complex. Several internal and external factors interact and lead to the problematic skin condition. Staphylococcus Aureus (S.aureus) is a bacterial strain known to worsen atopic dermatitis (Galli et al. 2020) and its colonization on the skin results from dysbiosis of the normal and healthy microbiota.

Acne vulgaris and atopic dermatitis are only examples of various skin conditions associated with microbiota dysbiosis. Establishing these associations of dysbiosis in skin diseases would strengthen skin-microbiota research and help to find sustainable treatment strategies for several skin conditions. Additionally, normalization of the skin microbiota in already well studied skin diseases would improve the clinical state of patients and would be an effective strategy in reconstituting a healthy microbiota after treatment if antibiotic use is necessary.

MIKROSKIN aims to provide an easy and quick tool to study microbiota dysbiosis in a research setting and as well in patients for selecting and monitoring treatment of various skin conditions. By targeting various bacteria at the same time the long-term aim is to create a high throughput test to detect dysbiosis in the skin microbiota.

Concept

The aim is to develop an aptamer-based rapid test that detects dysbiosis in the microbiota by inducing a color change in a semiquantitative manner.

What is an aptamer?

Aptamers are small RNA or ssDNA sequences that are about 100 nucleotides long. These short single-stranded nucleotide sequences can fold and form tridimensional structures. In this tridimensional state aptamers acquire recognition properties, meaning that they can bind to other molecules and targets. Using a technique called Systematic Evolution of Ligands by Exponential Enrichment (SELEX), aptamers are specifically selected and improved to bind only one specific target (Zhou and Rossi 2017). In our project we use SELEX to select aptamers targeting specific skin bacterial strains to determine their abundance on the skin and compare these results with the amount of total bacteria in our sample, where an aptamer targeting nearly all bacteria on the skin will be selected.

If you want to know more about the theory behind SELEX and the detailed protocol, click here

Detection Method

Our detection method is based on the colorimetric properties of Polydiacetylene (PCDA). PCDA can self-assemble into vesicles, which acquire colour-changing properties upon activation. External-stress, like heat, chemical or mechanical stress, induces a colour change from red to blue. It is possible to conjugate sensor molecules, like antibodies or aptamers to these vesicles, which in turn can sense binding of a specific target. This makes PCDA ideal as a biosensor (include ref: https://pubmed.ncbi.nlm.nih.gov/29462870/).

If you want to know more about the theory behind our detection method and the detailed protocol, click here

By targeting different skin bacterial strains with our aptamers, we get detailed information about their presence upon our skin. By comparing these results with an internal control, sensing nearly all skin bacteria, we can calculate a ratio and thus see the proportion of the skin bacterial strains. This enables us to detect dysbiosis in the skin microbiota fast and easily, without the need of expensive sequencing or slow bacterial cultivation.

We can expand our targets by the selection of new aptamers against additional bacterial strains or even antibiotic resistant strains. Our aim is to make MIKROSKIN a high throughput testing tool with customizable targets. Users should be able to choose the targets, which the test should detect, due to their specific needs. These adaptation possibilities make our rapid test MIKROSKIN a great tool for research and possibly also for clinicians and individuals.

Find out more about our stakeholders and implementation strategy, click here Link to Implementation

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Figure 1: Picture by Josh Withers on Unsplash

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