Using_TraDIS_to_investigate_antibiotic_combinations_in_ESKAPE_pathogens

Antibiotic combination therapy presents a rare opportunity to revive antibiotics from the clutches of resistant bacteria, yet currently there is little understanding of the molecular mechanisms underlying antibiotic synergy. Preliminary work described here and a few studies indicate that additional mechanisms of action (MOA) occur during synergistic killing beyond those of the original antibiotics. This work will use TraDIS to identify genes involved in multiple synergistic treatments and determine how bacterial cells gain resistance. TraDIS libraries of the ESKAPE pathogens Acinetobacter baumannii and Staphylococcus aureus and the model organism Escherichia coli will be grown with and without key combinations of antibiotics and using TraDIS analysis, genes involved in resistance and sensitivity will be identified for the first time.