Title:Membrane-Permeabilizing Activity of Reverse-Amide 2-Aminoimidazole Antibiofilm Agents Against Acinetobacter baumannii
VOLUME: 12 ISSUE: 2
Author(s):Sean D. Stowe, Richele J. Thompson, Lingling Peng, Zhaoming Su, Meghan S. Blackledge, G. Logan Draughn, William H. Coe, Eva Johannes, Valerie K. Lapham, John Mackenzie, Christian Melander and John Cavanagh
Affiliation:Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, North Carolina 27695, United States of America.
Keywords:2-aminoimidazole, Acinetobacter baumannii, biofilm, membrane permeabilization, reverse amide, SEM.
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.
