Targeted Antimicrobial Treatment of Acne Vulgaris by Engineered High Molecular Weight Contractile Nanotubes

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 DESCRIPTION (provided by applicant): Acne is a common dermatological condition, particularly amongst teenagers, with a large unmet medical need because of the rise of antibiotic-resistant bacteria and the significant side effects of current treatments. R-type bacteriocins, or "contractile nanotubes" (CNTs), are bactericidal proteins released by certain bacteria to confer a competitive advantage over related strains or other species. The receptor-binding protein in a CNT provides target specificity, working in concert with the contractile scaffold to puncture the target cell, depolarizing the membrane, causing ion leakage and ultimately cell death. Altering the receptor-binding protein can retarget the novel hybrid CNT to the target bacteria of choice. We will collaborate with AvidBiotics to utilize their CNT platform t engineer the receptor-binding domains specific for P. acnes, the primary opportunistic pathogen causally linked to acne, onto the contractile structural scaffolds of CNTs derived from Gram-positive bacteria such as C. difficile. We therefore aim to create novel hybrid CNTs that would only attack P. acnes. Success in this proof-of-concept proposal will lead to further development of these antimicrobial proteins as effective acne therapeutics superior to current treatments.