Project Background

Cutibacterium acnes (C. acnes) is a prevalent cause of skin infections and is the major causative agent in common acne vulgaris[1,2]. Cutibacterium acnes is one of the most common forms of acne, affecting over 45 million individuals in the United States alone, 9.4% of the world’s population, particularly adolescents. It is estimated that as many as 80% of adolescents develop acne, and 20% of all visits to the dermatologists are to seek care for acne. In addition to acneiform role, C. acnes is also implicated in other infections. As many as 10-40% of early postoperative infections have C. acnes as a causative agent. C. acnes is also found as a source in neurosurgical infections of ventricular shunts, the rate ranges from 1.5-38%. Addressing C. acnes infections is further complicated by a significant degree of antimicrobial resistance with some estimates that as many as 50.5% of patients with C. acnes were resistant to one or more antibiotics. Other infections caused by C. acnes include bone and joint infections, endocarditis and endophthalmitis [3-6]. Furthermore, acne vulgaris contributes to psychological distress, such as reduced mental health and self-esteem. This can further lead to the suffering of adolescents all across the United States. C. acnes, like several other bacteria, creates a protective biofilm on the skin, hindering the effectiveness of topical treatments for acne vulgaris. This makes infections more difficult to treat and prevents topical agents from being widely effective on C. acnes-induced acne. Biofilm is composed of microbial cells and extracellular polymeric substances (EPS). EPS, which is composed of 62.6% polysaccharides is quite hardy and affords protection of the bacteria. By manipulating the innate carbohydrate degradation of C. acnes, the degradation of the extracellular matrix through the decomposition of carbohydrates is promoted.

This study aims to genetically manipulate C. acnes biofilm by breaking down carbohydrates. This will be done by using a plasmid to produce the enzyme Phosphofructokinase, a catalyst of glycolysis. Since the biofilm is made up of over 50% carbohydrates, increasing the glycolytic activity of C. acnes by inserting a catalyst will allow for degradation of the biofilm. In the future, we aim to utilize a hydrogel to be our enzymatic transporter to administer this catalyst to C. acnes.

Proof of Concept:
Biofilm is proven to have a large impact on antibiotic effectiveness. Biofilm formation typically prevents antimicrobial efficacy, indicating that it provides shielding for acne[11]. On average, antibiotics take from 6-8 weeks to be effective on acne[12], whereas in the lab antibiotics take up to 48 hours. Biofilm is a large reason for this as it provides an extra layer of protection for the bacteria that prevents antibiotics from being effective. Another study shows that the glycolytic pathway is a regulator of biofilm formation in Saccharomyces cerevisiae, proving that PFKL can be used for biofilm degradation[13].

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