Antimicrobial-Membrane Interactions in Living Bacteria

With the support of the Chemistry of Life Processes (CLP) Program in the Division of Chemistry, Professor Hai-Lung Dai of Temple University is studying how bacterial membranes regulate their interactions with the surrounding environment, in particular those containing antimicrobial agents. The goal of this project is to provide fundamental knowledge that holds potential for future development of more effective antimicrobials that destroy disease-causing bacteria and reduce bacterial resistance to antibiotics.

The role of small molecules and synthetic proteins in changing the permeability of bacterial cell membranes will be studied by quantitatively examining the response of small molecules whose interaction with light allows for their very sensitive detection when bound to cell membrane components. This powerful light-based method will be used to test how tiny holes are formed in the membrane upon membrane interaction with nearby chemicals or by changing how molecules move through channels in the membrane of bacteria.

Professor Dai will integrate high school, college, and PhD students into the research program, providing a highly diverse group of students a very broad scientific skill set to help them pursue their career goals. Further broadening the impact of the project is a summer camp for Philadelphia inner city middle school students. In sum, the project will help strengthen the scientific workforce by training and exposing young minds to research aimed at providing answers to important fundamental questions about the chemistry of bacterial membranes with the ultimate goal of providing information key to addressing bacterial infections and antibiotic resistance.

The significance of the research area is evidenced by the growing problem of antimicrobial-resistant bacterial infections, which are predicted by the World Health Organization and the United Nations to result in the death of 10 million people annually by 2050.

In this study, Professor Dai will examine how the complex wall structures of bacteria exercise their regulatory functions on external molecules like antimicrobials. We will delineate, using both nonlinear optical spectroscopy and microscopy approaches, a variety of membrane transport mechanisms. These will include those based on import channels, efflux pumps, and lipid bilayer permeability, which play key roles in regulating intracellular concentrations of molecules critical to bacteria viability and protecting the bacteria from harmful compounds or an over-abundance of what would otherwise be thought to be useful compounds.

The research will provide fundamental understanding of how antimicrobials interact with the various components of bacterial membranes to make them more permeable and reduce the protective functions of the membrane. Experiments will be designed to gather data critical for understanding how membranes perform their regulatory functions for living cells, as well as for designing strategies for developing more effective antimicrobials.

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.