Team:Beijing 4ELEVEN/Description
Acne vulgaris, also known as acne, is often caused by hormone excretion of the human body during adolescence. These hormones promote sebum accumulation and therefore increase adherence of pathogenic bacteria including Propionibacterium acnes--a bacteria responsible for acne formation. The overproduction of P.acnes results in local inflammation. Nowadays, acne is often misbelieved in conventional wisdom to be a common puberty phenomenon which would eventually subside as maturity is reached. However, according to a survey, in about 85% of cases, acne follows its victims to adulthood[1]. Meanwhile, acne is rather a severe disease--even after its recovery, it leaves scars that require surgical means to remove[2].
Moreover, both acne and its scars have negative impacts on both their victims' mental and physical health[3]. Most studies that focus on stress and mental problems caused by acne suggest the onset or deterioration of acne is influenced by a number of neurogenic skin factors that interact with its pathogenesis. This two-way intimate relationship between skin and mind emphasizes the importance of holistic and interdisciplinary treatment for acne patients, which involves not only dermatologists but also psychologists and psychiatrists [4]. Therefore, we aim to find an effective and simple treatment of acne.
Figure 1. One of our teammates, Yuchu Wang, frustrated by acne
Antibiotic resistance of bacteria like P.acnes is recently caused by unnecessary and insufficient use of antibiotics. In other words, bacteria develop the ability to continue to grow after drugs designed to kill them are applied[5]. As the issue of microbial resistance is getting severe, there has been a great demand for an alternative of antibiotics. Antimicrobial peptides (AMPs) are peptides produced by all organisms to serve a fundamental role in innate immunity. As an important component of the innate immune system, AMPs provide immediately effective, non-specific defenses against infections. AMPs are attractive candidates for clinical development because of their selectivity, their speed of action and, most importantly, because bacteria may not easily develop resistance against them[6]. Therefore, AMPs are a great alternative for antibiotics at preventing antibiotic resistance.
Peptides up to 30 mer are normally more efficiently produced via chemical synthesis, while longer ones and proteins benefit from recombinant approaches. Although the costs may be lowered by a factor of a hundred, but the technical difficulties should not be underestimated. An estimated one million liters of fermentation mixture will be necessary to produce 100 kg of recombinant peptide through chemical synthesis, which is not very cost-effective for pharmaceutical companies[7]. Biosynthesis, using recombinant DNA techniques, could make commercial-scale synthesis feasible but the peptides are usually lethal to the micro-organisms used to produce them[6]. In our case, we choose to synthesize 5 acne curing AMPs which are only harmful to prokaryotes--CEN1HC-Br, GDP20, snake cathelicidin-BF, human cathelicidin LL-37, and tridecapeptide--with Pichia pastoris, an eukaryotic microbe.
Figure 2. One mechanism of AMPs killing bacteria.(Source: Bahar, A.A et al. Antimicrobial Peptides. 2013)
However, simply AMPs themselves are not quite enough for our idea of creating an applicable facial product. Looking at the project of 2019 GreatBay-SCIE StiKit, we found just the ingredient we were missing—adhesive and cohesive proteins. These proteins originated from mussel and barnacle feet, having potentials for waterproof bioglues and coating materials. When mixed together, adhesive proteins act like glue, helping to maintain interfacial adhesion, while cohesive proteins help maintain the shape of the mixture, enabling the formation of a layer of coating. Seeing in their project description that, “adhesive proteins are used as supplements to cover cuts and reduce leakage of blood after surgery”, we decided it feasible to use the proteins in their tool box to help make our product waterproof and long-lasting on the human skin.As our team went through their project design, we selected the fp1-mfp5-fp1, CsgA-mfp5, and CsgA-mfp5-mfp5 recombinant protein, consisting of the cohesive protein mfp1/CsgA and the adhesive protein mfp5, which is rendered by GreatBay_SCIE “very adhesive” and its yields “increase significantly”, to express using Pichia pastoris[8].
Figure 3. Structure and function of mussel foot proteins. (Source: Hwang, Dong Soo et al. Protein- and Metal-dependent Interactions of a Prominent Protein in Mussel Adhesive Plaques. 2010)
Our team aims to create a product consisting of two parts--AMPs solution and protein adhesive--that forms a thin waterproof film when applied to pimples, kills P.acnes, and restores beauty to its users.
Figure 4. An ideal demonstration of our product. The purple liquid represents AMPs and the blue gel-like substance represents the mixture of our adhesive and cohesive proteins.
[1] Hazarika, Neirita, and Radha K. Rajaprabha. "Assessment of life quality index among patients with acne vulgaris in a suburban population." Indian Journal of dermatology. 2016, 61, 163.
[2] Boen, M; Jacob, C. A Review and Update of Treatment Options Using the Acne Scar Classification System. Dermatol Surg. 2019,45,411.
[3] Layton AM. Disorders of sebaceous glands. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. 8th ed. Oxford: Wiley-Blackwell Publication. 2010, 42, 1–89.
[4] Jović, A.; Marinović, B.; Kostović, K.; Čeović, R.; Basta-Juzbašić, A.; Bukvić Mokos, The Impact of Pyschological Stress on Acne. Acta dermatovenerologica Croatica : ADC,2017, 25(2), 1133–1141.
[5] https://www.cdc.gov/drugresistance/index.html
[6] O’Neill, J. Antimicrobial peptides: Tackling of a crisis for the health and wealth of nations. Available online: http://amr-review.org/sites/fefault/files/AMR%20Review%20paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf
[7] Ramesh, S., de la Torre, B. G., Albericio, F., Kruger, H. G., & Govender, T. (2016). Microwave-Assisted Synthesis of Antimicrobial Peptides. Antimicrobial Peptides, 51–59. doi:10.1007/978-1-4939-6737-7_4
[8] https://2019.igem.org/Team:Greatbay_SCIE
[9] Bahar, A.A.; Ren, D. Antimicrobial Peptides. Pharmaceuticals 2013, 6, 1543-1575.
[10] Hwang, Dong Soo; Zeng, Hongbo et al. Protein- and Metal-dependent Interactions of a Prominent Protein in Mussel Adhesive Plaques. The American Society for Biochemistry and Molecular Biology, Inc. 2010.
