Our study aimed to analyse the responses of the clonal ST131 strain, containing the ESBL and multi-drug resistance plasmid under different beta-lactam and ciprofloxacin antibiotic stress in comparison with no antibiotic stresses in order to identify the specific response of a MDR plasmid to the specific antibiotic and the potential interaction between the plasmid and the host bacteria under different stresses. The aim was to understand how the plasmid and bacterial host proteins are influenced by the different antibiotic stresses. By analysing these factors systematically we aimed to identify the pathways and core or antibiotic specific responses of the bacteria. Using proteomics we provide an unbiased protein map of a pathogen with a MDR plasmid under antibiotic stress and compare it with the same bacteria in the absence of the stress.