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From 2014hs.igem.org

Project

Background

The Role of P. Acnes in Acne Vulgaris

The bacteria Propionibacterium acnes is responsible for the condition called Acne Vulgaris, more commonly known as acne. Although P. Acnes is not an issue for most people, there are certain virulent strains that exacerbate acne inflammation. The bacteria thrives in the presence of lipids, specifically sebum, which serves as the primary source of the bacteria's energy and sustenance. An increase of sebum production attracts bacteria into hair follicles, where the bacteria can multiply and colonize, resulting in an inflammatory reaction of cysts and pustules, which can lead to acne scars.

Description

For the 2014 Competition season, Montgomery_Cougars_NJUSA aims to create a better solution for acne reduction. Acne is a problem that affects nearly 80% of American adolescents. Unfortunately, this widespread problem does not have a concrete solution. Proactiv, a leading acne medication company, uses salicylic acid to burn off skin and bacteria alike from the patient’s face. This method is moderately painful and is not always 100% effective. So, to combat this widespread ailment, Montgomery iGEM has decided to take a different approach.

In an effort to create a less invasive treatment we decided to produce an enzyme to break down the sebum on human skin, thereby reducing the bacteria's source of energy and ability to colonize. Because sebum is made of of triglyceride oils, wax, squalene, and metabolites of fat-producing cells, we sought a group of enzymes that would break down these components. To counter each of these components, we have tracked down enzymes such as wax-ester hydrolase, triglyceride lipase, squalene monooxygenase, HMG CoA Reductase and Lipoprotein Lipase. Throughout the next few weeks, we plan to find genes that we can transform bacteria with to include these enzymes. Our final product will include genes that code for many of these enzymes, increasing our chance of reducing nutrients for acne-inducing bacteria.

Design

Gene Selection

Initially, we thought to create a cocktail of enzymes that would break down components of sebum (triglyceride oils, wax, squalene, and metabolites of fat-producing cells). However, as a new team, we decided that choosing one enzyme would be the most practical.

Genes that Code for Enzymes to Break Down Components Sebum

Enzyme	Gene
Triglyceride Lipase-lipases that hydrolyse ester linkages of triglycerides	PNPLA2 gene provides instructions for making an enzyme called adipose triglyceride lipase
Triacylglycerol Lipase: the fat-splitting enzyme in pancreatic juice; it hydrolyzes triacylglycerol to produce a diacylglycerol and a fatty acid anion triacylglycerol + H2O diacylglycerol + a carboxylate	LIPC gene encodes hepatic triglyceride lipase
Squalene epoxidase is an enzyme released by the dermatophyte fungi to break down Squalene.	SQLE gene: encodes squalene epoxidase
HMG CoA Reductase: an enzyme that catalyzes the production of mevalonate from HMG CoA. It is a rate controlling enzyme in the mevalonate pathway that regulates the synthesis of cholesterol and other isoprenoids.	HMGCR
Lipoprotein Lipase - water soluble enzyme that hydrolyzes triglycerides into two fatty acids.	LPL gene

References

Bhatia A, Maisonneuve JF, Persing DH. PROPIONIBACTERIUM ACNES AND CHRONIC DISEASES. In: Institute of Medicine (US) Forum on Microbial Threats; Knobler SL, O'Connor S, Lemon SM, et al., editors. The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects: Workshop Summary. Washington (DC): National Academies Press (US); 2004.

Higaki, Shuichi. "Lipase Inhibitors for the Treatment of Acne." Journal of Molecular Catalysis B: Enzymatic 22.5-6 (2003): 377-84. Print.