Potent Killing of Pseudomonas aeruginosa by an Antibody-Antibiotic Conjugate
Kimberly K. Kajihara, Homer Pantua, Hilda Hernández-Barry, Meredith Hazen, Kiran Deshmukh, Nancy Chiang, Rachana Ohri, Erick R. Castellanos, Lynn Martin, M Matsumoto, Jian Payandeh, Kelly M. Storek, Kellen Schneider, Peter A. Smith, Michael F. T. Koehler, Siao Ping Tsai, Richard Vandlen, Kelly M. Loyet, Gerald Nakamura, Thomas H. Pillow, Dhaya Seshasayee, Sharookh B. Kapadia, Wouter L. W. Hazenbos
Abstract
assays, affirming the need for new therapeutic approaches. Antibiotics often fail in the preclinical stage due to insufficient efficacy against P. aeruginosa. One potential strategy is to enhance the local concentration of antibiotics with limited inherent anti-P. aeruginosa activity. This study presents proof of concept for an antibody-antibiotic conjugate, which releases a high local antibiotic concentration inside macrophages upon phagocytosis, resulting in potent intracellular killing of phagocytosed P. aeruginosa bacteria. This approach may provide new therapeutic options for antibiotics that are dose limited.