Vanessa Schmidt

The opportunistic pathogen Pseudomonas aeruginosa uses a cell-to-cell communication system called quorum sensing to regulate virulence factors and antibiotic resistance mechanisms. The LasR-I system, a key component of quorum sensing in P. aeruginosa, consists of the LasR transcriptional regulator and LasI signal synthase which produces the signaling molecule 3OC12-HSL. While LasR is important for virulence and antibiotic resistance, paradoxically, LasR-deficient mutants are commonly found in clinical infections of antibiotic-treated patients. Previous work in our lab revealed that a mutation in the ribosome accessory factor EF-G1A can reverse how quorum sensing affects antibiotic resistance - while disrupting LasR typically decreases resistance in wild-type strains, it increases resistance in strains with an EF-G1A mutation.  The goal of my research is to understand the complex relationship between quorum sensing and antibiotic resistance in P. aeruginosa, specifically focusing on how mutations enable bacteria lacking a functional quorum sensing system to persist under antibiotic pressure in clinical settings. Through this work, I aim to identify and characterize mutations that allow bacteria to maintain antibiotic resistance even when their quorum sensing system is impaired - a paradox commonly observed in clinical infections but poorly understood mechanistically. Using a combination of experimental evolution and genome-wide screening approaches, this work will reveal how bacteria can adapt to overcome their typical reliance on quorum sensing for antibiotic resistance. Understanding how adaptive mutations influence the relationship between quorum sensing and antibiotic resistance will provide crucial insights for developing novel therapeutic strategies targeting P. aeruginosa infections. This research is significant as antimicrobial resistance continues to emerge as a major public health threat, with P. aeruginosa being particularly concerning due to its multi-drug resistance and ability to cause severe infections in immunocompromised patients.