Monoclonal therapeutic antibody synergizes with antibiotics to promote clearance of Pseudomonas aeruginosa 3062

Abstract Description Pseudomonas aeruginosa is a ubiquitous, opportunistic Gram-negative pathogen. It is a prevalent hospital-acquired pathogen, and possesses multi-drug resistance (MDR), resulting in difficult to treat infections. The CDC has highlighted the need for novel strategies to combat these MDR strains of P. aeruginosa, and improve the efficacy of treatments for patients. Standard-of-care antibiotics (ABX) can be supplemented with novel therapies, like monoclonal antibodies (mAbs), to improve therapeutic efficacy. Our lab has generated one such mAb, WVDC-0496, that operates in a non-classical function. WVDC-0496 can kill bacteria directly, without the need for additional immune components. This mAb confers 100% therapeutic protection of mice in lethal sepsis infection of P. aeruginosa. We hypothesize that WVDC-0496 will synergize with ABX, decreasing bacterial viability at sub-efficacious concentrations if the ABX or mAb were alone. To assess this, we developed a checkerboard assay that could measure potential synergistic or antagonistic interactions between the mAb and representative ABX. Synergy was observed between WVDC-0496 and several ABX family representatives. In addition, we performed mRNA sequencing and membrane flux analyses to determine the mechanism of action of WVDC-0496. By improving the therapeutic efficacy of standard-of-care antibiotics and its novel function, WVDC-0496 could provide alternatives against MDR pathogens. Funding Sources Supported by NIH 1R01AI180050-01A1 and the WVU STEM Fellowship for Graduate Research Assistants Topic Categories Vaccines and Immunotherapy (VAC)