Immediate efficient antibiotic therapy is the key to improve patient survival during infection. However, the identification of appropriate antibiotics in a timely manner, is challenging due to resistant bacterial strains. The periplasmic chaperone SurA is a crucial factor for outer membrane integrity and virulence of many Gram- pathogens, especially with regards to complement resistance and antibiotic susceptibility. By inhibition of SurA, we aim to create an effective new treatment option to fight against Gram- bacterias. We focus on Acinetobacter baumannii (Ab) and two representative SurA orthologs from carbapenem-resistant Pseudomonas aeruginosa (Pa) and Klebsiella pneumoniae (Kp), following a highly integrative approach. We will employ an established screening assay to identify SurA inhibitors, and solve crystal structures of SurA in complex with candidate inhibitors. This will be amended by in silico screening, forming the basis for lead development by medicinal chemistry.

2020

2022