Combining Cell Envelope Stress Reporter Assays in a Screening Approach to Identify BAM Complex Inhibitors
Maurice Steenhuis, Federico Corona, Corinne M. ten Hagen‐Jongman, Waldemar Vollmer, Dominique Lambin, Philippe Selhorst, Hugo Klaassen, Matthias Versele, Patrick Chaltin, Joen Luirink
Abstract
and Rcs stress responses, while not inducing the intracellular heat-shock response. Two of the five compounds (compounds 2 and 14) showed the characteristics of known BAM complex inhibitors: synergy with OMP biogenesis mutants, decrease in the abundance of various OMPs, and loss of OM integrity. Importantly, compound 2 also inhibited BAM-dependent OMP folding in an in vitro refolding assay using purified BAM complex reconstituted in proteoliposomes.
Topics & Concepts
BiogenesisCell envelopeBacterial outer membraneEscherichia coliIntracellularMutantBiologyBacteriaVirtual screeningChemistryBiochemistryCell biologyBiophysicsDrug discoveryGeneticsGeneBacterial Genetics and BiotechnologyAntibiotic Resistance in BacteriaBacteriophages and microbial interactions