Taylor Duval

P. aeruginosa is a gram-negative bacterium that is a major cause of hospital-associated infections, often leading to fatal outcomes in immunocompromised patients. Due to the emergence of antibiotic-resistant bacteria, clinicians are sometimes forced to rely on antiquated drugs such as polymyxins, considered a last resort therapeutic due to their propensity for kidney injury. To reduce the toxicity of Polymyxin B and novel antimicrobial therapeutics, we propose the development of an antibody-antimicrobial conjugate (AAC), a therapeutic molecule that links an antibiotic with an antibody (a protein produced by the immune system to fight off harmful substances). We will attach Polymyxin B to a P. aeruginosa-specific antibody, which will carry the drug directly to the infection site. Drug release will be triggered by enzymes that are amplified at the infection region. Due to the improved targeting, less drug will be required to clear the infection, in turn reducing or eliminating toxic side effects. This AAC approach will also be used to accommodate other novel or abandoned drugs, allowing us to engineer less toxic and more efficient therapeutics against potent bacterial or fungal threats.