Background

Why did we choose S. aureus to be our Target?

Staphylococcus aureus is a Gram-positive bacterium and a common human pathogen. Approximately 30% of the world population normally are colonized with S. aureus. It commonly appears on human skin. S. aureus does not cause infection on healthy skin but can cause serious infections such as furuncles, carbuncles, or impetigo when entering deeper layers of skin through a cut as a scratch.

Fig.1 Staphylococcus aureus, furuncles, carbuncles and impetigo

Statistics of S. aureus and its Infections

According to WHO statistics, there is 35.86% of bloodstream infection due to methicillin-resistant Staphylococcus aureus (MRSA) among patients seeking care.
According to the “Carbuncle Treatment Market Analysis”, we can know that this disease is spread all over the world. In the aspect of market demand, the carbuncle treatment is worth developing.
Moreover, there are 140 million people including 100 million children in the world who have impetigo.

Furuncles and Carbuncles

Motivation

As the highly contagious superficial bacterial skin disease spread by S. aureus around the world, Methicillin-Resistant Staphylococcus aureus (MRSA) is also making a great impact globally. Take Impetigo, one of the infections of S. aureus, for example, if we want to get a rapid treatment nowadays, we may choose to apply antibiotics or get an injection. However, here comes a few questions. Are those treatments that may lead to producing MRSA and getting pain really suitable for infants who take a large part of the patient percentage of S. aureus infections? Moreover, S. aureus infections can not only make a skin disease but also lots of severe complications. Is there any treatment that can sterilize S. aureus at an early stage without making symptoms worse because of the drug resistance of S. aureus?

This year, to reduce the overuse of antibiotics and provide an easy-to-use treatment for everyone in the world, NTHU_Taiwan developed an innovative multi-functional dressing that can achieve simplicity, painless, low cost, and safety by using the antimicrobial peptide complex (AMPC) and the microneedle system (MNs)..

Approach

Antimicrobial Peptide Complex (AMPC)

The common treatment for these skin infections is antibiotic therapy which may cause drug resistance of bacteria. To find out a better treatment, we choose antimicrobial peptides (AMPs). The AMPs used in this study are parts of the human immune system that can kill bacteria without leading to drug resistance.

Getting insight into V8 protease, most pathogenic Staphylococcus aureus secrets an extracellular protease named V8 protease, which has a cleavage site at glutamic acid (E) and aspartic acid (D). Thus, we came out with the idea that joining antimicrobial peptides (AMPs) with V8 protease cleavage site containing linkers to form a peptide complex, AMPC. The AMPC is inactive but can be activated upon cleavaged by V8 protease. This is just the first step of our project to reach the goal of the specific killing of S. aureus.

Fig.2 The cleavage site concept (Click ☝ )

Fig.3 The concept of our project (Click ☝ )

See Experiments page for detail information.

Microneedle System

Different from the subcutaneous injection apparatus, a microneedle patch, is a multi-functional dressing with micron-sized needle tip structures. Microneedle patches have been used in interstitial fluid (ISF) detection and drug delivery. In this project, we use it as an applicator, which is painless, convenient, easy-to-use, and can penetrate the epidermis to the depth of the wound. Furthermore, the material we use for this patch such as gelatin and Hyaluronic Acid Methacrylate (HAMA) has high biocompatibility without provoking allergic reactions. In the second process to specifically kill S. aureus, we designed an innovative microneedle system. The outer layer HAMA coating of our microneedle patch can be degraded by S. aureus secreted hyaluronidase and can release the AMPC to kill S. aureus specifically.

Fig.4 Microneedle Patch (Click ☝ )

Fig.5 Microneedle Patch (Click ☝ )

See Hardware page for detail information.

Reference

Boils and carbuncles - Symptoms and causes. (2021, September 18). Mayo Clinic. Retrieved October 12, 2022, from https://www.mayoclinic.org/diseases-conditions/boils-and-carbuncles/symptoms-causes/syc-20353770
Higuera, V. (2020, February 21). What’s the Difference Between a Furuncle and a Carbuncle? Healthline . Retrieved October 12, 2022, from https://www.healthline.com/health/furuncle-vs-carbuncle
Indicator Details . (n.d.). Retrieved October 12, 2022, from https://www.who.int/data/gho/data/indicators/indicator-details/GHO/sdg-3.d.2-amr-infect-mrsa
InformedHealth.org [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2006-. Boils and carbuncles: Overview. 2018 Jun 14. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513141/
Kwiecinski JM, Horswill AR. Staphylococcus aureus bloodstream infections: pathogenesis and regulatory mechanisms. Curr Opin Microbiol. 2020 Feb;53:51-60. doi: 10.1016/j.mib.2020.02.005. Epub 2020 Mar 12. PMID: 32172183; PMCID: PMC7244392.
Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022 Feb 12;399(10325):629-655. doi: 10.1016/S0140-6736(21)02724-0. Epub 2022 Jan 19. Erratum in: Lancet. 2022 Oct 1;400(10358):1102. PMID: 35065702; PMCID: PMC8841637.