Development of EcDsbA Inhibitors Using Fragment-Based Design Strategies

Antibacterial resistance is a major global health problem causing an increasing number of deaths worldwide. We are now observing bacterial resistance to the majority of available antibiotics. Blocking bacterial virulence without causing the death of bacteria exerts less evolutionary pressure for the selection of bacterial resistance and could lead to an effective antibacterial therapy. EcDsbA is an enzyme that facilitates an important pathway for the activity and stability of virulence determinants. This thesis reports the development of small molecule inhibitors of EcDsbA, which are hypothesised to show antivirulence effects.