In 2013 drug resistance in bacteria & the failure to develop antibiotics was placed on the National risk register. In addition to genetically acquired resistance to antibiotics, if bacteria enter a slow-growing or dormant state then they will also resist antibiotics which target biosynthetic pathways of the cell metabolism. Examples include biofilm-mediated hospital infections, in which the bacterial cells exist in an energy-deprived environment and tuberculosis, in which the cells can become dormant.
This has led to an interest in alternative control strategies, that target the bacterial membrane. These include cationic antimicrobial peptides (AMP), which are part of the innate immune system, the increased use of copper surfaces in hospitals, and the use of positively charged polyelectrolytes as biocidal surface coatings.
At present there is not a complete understanding of the underlying mechanisms of these different membrane-targeting antimicrobial strategies. Experiments carried out in our research group suggest that antimicrobial action can be linked to the physical properties of the bacterial membrane, specifically the membrane fluidity, and that a connection exists to the cell's metabolism and use of energy via the transmembrane potential. Our goal is for the mechanistic insights from a new biophysical approach to direct the interventions that will avert the scenario identified by the CMO, which would have dreadful implications for wellbeing, particularly in later life.
In this project neutron reflectivity experiments from floating bilayer mimetics for bacterial membranes will be used to investigate at the molecular level the influence of membrane potential on the binding of antimicrobial peptides. Fluorescence microscopy techniques will be used to measure the membrane potential in single cell experiments. Combining these approaches will enable the investigation of whether an interplay between energy sources in the cell, antimicrobial binding and the effect of antimicrobials can provide an explanation for the effectiveness of different antimicrobials in controlling bacterial growth.
- Dr Simon Titmuss (School of Physics & Astronomy, University of Edinburgh)
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