title: Identification of BfmR, a response regulator involved in biofilm development, as a target for a 2-Aminoimidazole-based antibiofilm agent.
abstract: 2-Aminoimidazoles (2AIs) have been documented to disrupt bacterial protection mechanisms, including biofilm formation and genetically encoded antibiotic resistance traits. Using Acinetobacter baumannii, we provide initial insight into the mechanism of action of a 2AI-based antibiofilm agent. Confocal microscopy confirmed that the 2AI is cell permeable, while pull-down assays identified BfmR, a response regulator that is the master controller of biofilm formation, as a target for this compound. Binding assays demonstrated specificity of the 2AI for response regulators, while computational docking provided models for 2AI-BfmR interactions. The 2AI compound studied here represents a unique small molecule scaffold that targets bacterial response regulators.
authors.affiliation: Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27695, USA.
authors.forename: Richele J
authors.initials: RJ
authors.lastname: Thompson
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Bobay
authors.forename: Sean D
authors.initials: SD
authors.lastname: Stowe
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Olson
authors.forename: Lingling
authors.initials: L
authors.lastname: Peng
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Su
authors.forename: Luis A
authors.initials: LA
authors.lastname: Actis
authors.forename: Christian
authors.initials: C
authors.lastname: Melander
authors.forename: John
authors.initials: J
authors.lastname: Cavanagh
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000254:growth & development; D001426:Bacterial Proteins / Q000737:chemistry / Q000502:physiology*; D018441:Biofilms / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D018613:Microscopy, Confocal; D008958:Models, Molecular
chemical_list: D001426:Bacterial Proteins; D007093:Imidazoles; C014973:2-aminoimidazole