Structural characterization of Propionibacterium acnes virulence factors

Acne is the most common skin disorder worldwide, affecting approximately 80 per cent of individuals at some point in their lives. How the skin develops this inflammatory condition is not entirely understood, nor is there a cure for severe, persistent cases of acne that often result in permanent scarring. Antibiotics are often prescribed as a first-line treatment, but the most effective antibiotic (Accutane) is known to have serious side effects, including birth defects and depression. In addition, antibiotic resistance is a growing problem. Propionibacterium acnes is present on most people’s skin and is the principal microorganism associated with acne. It can behave as an opportunistic pathogen under certain circumstances, expressing genes that lead to symptoms of acne. The genome of the bacterium has been sequenced and research has shown several genes that can generate enzymes for degrading skin, and proteins that may activate the immune system, leading to the initiation of acne, its development into inflammatory lesions and scarring. Angel Yu is focusing on O-sialoglycoprotein endopeptidase, a skin tissue-degrading enzyme. In order to understand how this protease works and how it recognizes its protein targets, she is growing crystals of the enzyme and using X-ray crystallography to study its structure at the atomic level. She will conduct studies that confirm the enzyme’s biological function and identify associated amino acid residues. Ultimately, Yu hopes her findings will provide insight into the molecular mechanism of this inflammatory skin disorder and identify new leads for the treatment of acne.