Molecular evolution of Small Multidrug Resistance transporters

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

This research project will lead to a fundamental understanding of how bacterial proteins adapt and change in response to chemicals and antibacterial compounds introduced by humans. Antiseptic handsoaps and cleaning agents are commonly used to control bacteria that cause disease. Bacteria possess proteins to resist these antiseptics. The goal of this project is to understand how these antiseptic resistance proteins work. In addition, this research will address how antiseptic resistance proteins change over time when bacteria are exposed to antiseptics. This project will support the laboratory training of a postdoctoral scholar and undergraduate students. An additional goal of this project is to develop a museum exhibit at the University of Michigan Natural History Museum. Visitors to the museum exhibit will learn about how antiseptic resistance spreads among bacteria. This museum exhibit will inform members of the public about the project’s research findings. This project addresses the molecular evolution of the Small Multidrug Resistance (SMR) family of membrane proteins, which efflux quaternary ammonium antiseptics. Integral membrane proteins experience a vastly different set of physical parameters than soluble proteins, and thus the evolutionary pressures acting on membrane proteins are also very different. Current understanding of how membrane proteins evolve increasing structural and mechanistic complexity, and how they evolve new transport functions, is limited. This research addresses these questions by applying a combination of phylogenetic, biophysical, and x-ray crystallographic approaches. Specifically, this project will analyze the biophysical basis for quaternary ammonium antiseptic export by SMR proteins (objective 1), the historical evolutionary events that lead to quaternary ammonium and polyamine export (objective 2). These lines of research are broadly relevant to ongoing evolution of bacteria in response to quaternary ammonium antiseptics, to which SMR proteins provide resistance. In objective 3, the investigators will translate the research findings regarding the interplay of SMR proteins bacterial antiseptic resistance to an audience of the general public using a museum exhibit at the University of Michigan Museum of Natural History. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.