The rise of antimicrobial resistance requires novel antibiotics with unexploited modes of action. Promising templates could be antibiotics that target Lipid II, known as the Achilles' heel of bacteria, at an irreplaceable pyrophosphate group. Such antibiotics, like nisin, plectasin, or teixobactin [1-3] would kill the most refractory pathogens without causing resistance. However, due to the challenge of studying small membrane-embedded drug-receptor complexes in native conditions, the structural correlates of the pharmaceutically relevant binding modes are unknown.
Here, using modern solid-state NMR methods that enable atomic-resolution studies in native bacterial membranes, we report on the physiologically relevant binding modes of several Lipid II-binding antibiotics.[4-5]
 Breukink et al, Science 2006
 Schneider et al., Science 2010
 Ling et al., Nature 2015
 Medeiros¬-Silva et al., Nature Communications 2018  Shukla et al., Nature Communications 2020