Grant: Discovery Grants Program - Individual

We now know that traditional antibiotics are losing their effectiveness against ever-evolving bacteria. This fact is because traditional antibiotics work against specific targets within the bacterial cell, and with bacterial mutations over time, the antibiotic no longer works as well. Now, researchers are looking at other areas of nature for help, including antimicrobial peptides. These are short proteins that are part of the immune systems of many animals, and some of the peptides attack bacteria directly at the membrane of the cell, causing the bacterium to rupture and die. Since the membranes of most bacteria share common structural features, and these features are unlikely to evolve much, these peptides should effectively kill many types of bacteria without so much evolved resistance. But why do these peptides kill bacterial cells, but not the cells of the host animal? For Gram-negative bacteria, the most likely reason is that their outer membrane is made of lipopolysaccharides, which is very different from an animal cell membrane. At this point, what we know about how these peptides work was likely done with models of animal cell membranes, and not with the more complex lipopolysaccharides. If we want to make better peptides, ones that we can use to fight all types of infection, we need a more accurate molecular picture of how they work. This research applies neutron diffraction to measure the structure of lipopolysaccharides and antimicrobial peptides together in action, the result of which will be a 3D atomic model of how these peptides work. We can then compare our picture with what biochemists have come to understand makes for a good antibiotic peptide, and hopefully design better treatments for bacterial infections.