Priscilla C. Olsen, Ph.D.

Research

The Olsen lab (Laboratory of Immunological Studies – LEI) specializes in developing novel therapies for bacterial infections, arboviruses, and allergic inflammatory lung diseases. Currently, our research focuses on characterizing the humoral immune response against multidrug-resistant (MDR) bacteria to facilitate the discovery of potent monoclonal antibodies. Antimicrobial-resistant bacteria have evolved sophisticated mechanisms to circumvent the pressure imposed by traditional antibiotics. Among these, the overexpression of efflux pumps stands out as a primary resistance strategy. By actively reducing intracellular drug concentrations, these pumps not only neutralize specific treatments but also provide a survival advantage that facilitates the development of secondary resistance mechanisms. The LEI group targets outer membrane proteins (OMPs)—the critical structural components of these Gram-negative efflux systems. Our research investigates the efficacy of human and murine antibodies designed to bind specifically to extracellular OMP epitopes, sterically block the efflux channel, revert the resistance phenotype by restoring antibiotic accumulation, and eliminate MDR pathogens through targeted neutralization.

Partnership Award

With the Partnership Award, Priscilla Olsen, Ph.D., and Beatriz Patricio, Ph.D., will team up to develop and test a new strategy to overcome antimicrobial drug resistance. An important driver of resistance is the overexpression of efflux pumps that expel antibiotics. Although recognized as a promising therapeutic target, this resistance mechanism remains relatively underexplored. This work aims to block efflux pumps using antibodies against TolC, one of the key components of efflux pumps associated with bacterial multidrug resistance. TolC antibodies will be linked to a liposome designed to bind to bacterial cell membranes and carry antibacterial drugs. The project combines Olsen’s experience in antibody-based immunology with Patricio’s expertise in nanotechnology to provide a proof of concept for this “resistance-reversing” drug delivery method. Their aim is to deliver antibiotics directly into bacterial cells, enhancing drug accumulation within the cells and limiting off-target effects. If successful, this approach could be an effective way to treat difficult infections and combat antimicrobial resistance.