Organisational Principles of the Bacterial Outer Membrane

Over a million deaths a year are attributed to antimicrobial resistant (AMR) infections, potentially growing to tens of millions by 2050, making the design of new antibiotics essential for global health. However, many AMR bacteria have a layer of extra protection from drugs called the outer membrane (OM). The OM is a mixture of phospholipids, lipopolysaccharides, lipoproteins and outer membrane proteins (OMPs), and how these components are organised has been a problem for microbiologists since the 1960s. Recent biophysical advances have opened possibilities for studying this long-standing problem from new perspectives. We now know OM function depends on mechanical strength, stiffness, impermeability and low fluidity. Atomic force microscopy (AFM) has shown abundant OMPs form a cell-wide lattice throughout the E. coli OM and super-resolution fluorescence microscopy (SRFM) has shown other OMPs form enriched islands within this lattice. However, the role of specific proteins in maintaining the lattice, the relationship between lattice formation and island formation, and how the biophysical properties of the OM affect cell division is not known. This project combines AFM and SRFM with genetics and biochemistry to develop new methods to answer these questions. By better understanding this important barrier, better OM compromising antimicrobials can be designed.