Membrane-Permeabilizing Activity of Reverse-Amide 2-Aminoimidazole Antibiofilm Agents Against Acinetobacter baumannii

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:

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.

Cite this article as:

Stowe D. Sean, Thompson J. Richele, Peng Lingling, Su Zhaoming, Blackledge S. Meghan, Draughn Logan G., Coe H. William, Johannes Eva, Lapham K. Valerie, Mackenzie John, Melander Christian and Cavanagh John, Membrane-Permeabilizing Activity of Reverse-Amide 2-Aminoimidazole Antibiofilm Agents Against Acinetobacter baumannii, Current Drug Delivery 2015; 12 (2) . https://dx.doi.org/10.2174/1567201811666140924125740