Biophysical Society Conference | Tahoe 2024

Molecular Biophysics of Membranes

Monday Speaker Abstracts

COMPUTATIONAL MICROBIOLOGY OF THE E. COLI OUTER MEMBRANE: A NEW PICTURE IS EMERGING Syma Khalid ; 1 University of Oxford, Biochemistry, Oxford, United Kingdom The cell envelope that surrounds Gram-negative bacteria is composed of two membranes (the inner and outer) which are separated by an aqueous region known as the periplasm. Together these three regions provide the bacterium with a formidable defence against unwanted incoming molecules, including antibiotics. The outer membrane contains a range of beta-barrel proteins of varying sizes and functions and in terms of its lipidic composition, it has lipopolysaccharides (LPS) in the outer leaflet and phospholipids in the inner leaflet. We are using multiscale simulations in combination with the experimental work (including native mass spectrometry, cross-linking studies and AFM) of our colleagues to develop a picture of the spatial organisation of the outer membrane of E. coli. Our work has shown that outer membrane proteins (OMPs) are not uniformly distributed throughout the membrane but occupy high protein density regions or ‘OMP islands’. These islands are separated by regions of high LPS (upper leaflet) and phospholipid (lower leaflet), in which there are hardly any proteins. We provide details of our current view of the organisation of OMP islands and briefly describe how this is being incorporated into our efforts to study antimicrobial penetration into the outer membrane and how this in turn, impacts the properties of the outer membrane Overall, our studies are now revealing a very different picture of the E. coli surface than the one presented in textbooks.

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