A lesson in efficient killing from two-component lantibiotics.

The combined activity of the constituents of two-component antibiotic systems is always significantly higher than the sum of the activities of the individual pieces. Understanding the principles behind this phenomenon might provide new ways to design new antibiotics. In this issue of Molecular Microbiology, Wiedemann and coworkers have made a big step towards understanding the mechanism of action of the two-component lanthionine-containing antibiotic lacticin 3147. It has now become clear that this two-component system specifically targets the bacterial cell wall precursor Lipid II. This makes this essential bacterial lipid one of the most sought-after targets in nature. Surprisingly, in view of its small size (MW 1875 Da), this is now the fifth different way that this key molecule is known to be targeted.