title: Membrane-permeabilizing activity of reverse-amide 2-aminoimidazole antibiofilm agents against Acinetobacter baumannii.
abstract: Acinetobacter baumannii has quickly become one of the most insidious and prevalent nosocomial infections. Recently, the reverse-amide class of 2-aminoimidazole compounds (RA-2AI) was found both to prevent A. baumannii biofilm formation and also to disperse preexisting formations, putatively through interactions with cytosolic response regulators. Here we focus on how this class of antibiofilm agent traverses cellular membranes. Following the discovery of dosage-dependent growth rate changes, the cellular effects of RA-2AI were investigated using a combination of molecular assays and microscopic techniques. It was found that RA-2AI exposure has measureable effects on the bacterial membranes, resulting in a period of increased permeability and visible structural aberrations. Based on these results, we propose a model that describes how the structure of RA-2AI allows it to insert itself into and disrupt the fluidity of the membrane, creating an opportunity for increased molecular permeability.
authors.forename: Sean D
authors.initials: SD
authors.lastname: Stowe
authors.forename: Richele J
authors.initials: RJ
authors.lastname: Thompson
authors.forename: Lingling
authors.initials: L
authors.lastname: Peng
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Su
authors.forename: Meghan S
authors.initials: MS
authors.lastname: Blackledge
authors.forename: G Logan
authors.initials: GL
authors.lastname: Draughn
authors.forename: William H
authors.initials: WH
authors.lastname: Coe
authors.forename: Eva
authors.initials: E
authors.lastname: Johannes
authors.forename: Valerie K
authors.initials: VK
authors.lastname: Lapham
authors.forename: John
authors.initials: J
authors.lastname: Mackenzie
authors.forename: Christian
authors.initials: C
authors.lastname: Melander
authors.affiliation: Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, North Carolina 27695, United States of America. john_cavanagh@ncsu.edu.
authors.forename: John
authors.initials: J
authors.lastname: Cavanagh
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects*; D000577:Amides / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D003428:Cross Infection; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests
chemical_list: D000577:Amides; D000900:Anti-Bacterial Agents; D007093:Imidazoles; C014973:2-aminoimidazole