What is it about?
Microbes which cause diseases have multiple strategies to combat immune responses. One strategy used by Staphylococcus aureus bacteria, which causes several infections, involves producing toxins which punch holes in the membranes of nearby white blood cells. The hole-producing mechanism is known to involve two toxic proteins called LukS and LukF which bind to a human membrane "receptor" protein called hC5aR. However, the relative number of these proteins required to make a hole in living cells has remained unclear. Here we use advanced fluorescence microscopy to track these proteins as they form holes in live cell membranes and use their brightness to determine how many are involved. We find that once a hole is form the structure to which the hole has form (the "receptor") is released as so is in effect recycled so that it can be used to form additional new holes. In this way the toxin has a far more dramatic killing effect on the cell. This effect may free up receptors to amplify inflammatory reactions in early stages of bacterial infections and have important implications for several other similar toxins and the design of new antibiotics. This adds important insight into mechanisms by which bacteria evade immune responses.
The following have contributed to this page: Professor Mark C Leake and Adam Wollman