(609a) Engineering Filamentous Phages to Deliver Antibacterial Cargo

Increasing antimicrobial resistance in bacterial pathogens has prompted a renewed interest in alternative approaches such as phage therapy. We are developing a platform for controlled phage therapy using engineered filamentous phages to delivery nanomaterials or antibiotics. The use of a model phage, M13, allows genetic engineering for binding specificity and biosafety. Chemical conjugation of nanoparticle or antibiotic cargo determines the localized effect. For example, phages carrying gold nanorods exhibit bacterial binding and controlled photothermal activation for efficient cell-killing. Studies in our group have validated the safety and efficacy of this approach using in vitro studies as well as a mouse model of Pseudomonas aeruginosa wound infection. In particular, wounds infected with a bacterial strain resistant to last-line antibiotics could be successfully treated using the phage-gold nanorod conjugates. In another approach, we engineer M13 to enhance delivery and specificity of antimicrobials that have toxic side effects, such as polymyxin B. In one case, the phage-drug conjugates lowered the required antibiotic concentration by almost two orders of magnitude. These findings point toward potential therapeutic strategies to treat bacterial infections.