Simulations contribute to study on critical bacterial outer membrane protein
Molecular dynamics simulations by Dr Phillip Stansfeld in the lab of Professor Mark Sansom have helped to reveal how bacteria construct a barrier against antibiotics and the body's immune system.
This player requires Flash or an HTML 5 capable browser
Movie illustrating the simulated opening of the side-gate of the LptDE structure through which lipopolysaccharide is inserted into the membrane. Copyright Phillip Stansfeld
These fortifications are found in Gram-negative bacteria which cause many different infections including salmonella, pseudomonas and meningitis. By impeding the construction of this barrier, it might be possible to tackle antibiotic-resistant bacteria.
Dr Stansfeld provided molecular dynamics simulations for a structural study carried out by groups from the University of East Anglia and Diamond Light Source. The researchers have published their work in Nature (1).
They describe the first crystal structure of the unique membrane lipopolysaccharide translocon in these bacteria. The LptD-LptE complex builds up the outer membrane, acting as a biological ‘bricklayer’ that pulls up the lipopolysaccharide 'bricks' from inside the bacterium to insert them in the outer membrane.
Simulations of the LptD-LptE complex helped the researchers understand the lipopolysaccharide translocation mechanism by indicating how the barrel within the translocon opens to allow membrane insertion.