Bacterial toxin-antitoxin modules

The major emphasis of our group is on bacterial TA modules. These are operons encoding a stable toxin and a labile antidote. They play a major role in bacterial stress physiology by temporarily halting cell division when nutrients are scarce. They are proposed to be involved in multidrug resistance. We have characterized in detail the biophysical and biochemical properties of the proteins belonging to the E. coli ccdAB and mazEF TA systems. This led to the elucidation of the first crystal structure of a TA toxin (CcdB), the first structure of a toxin:target complex (CcdB bound to a relevant fragment of gyrase) and the first structure of a TA antidote (MazE). Ongoing research in this field focuses on interactions between toxins and antidotes, on interactions of the antidotes and toxin:antidote complexes with DNA and on the ribonuclease activity of the toxin MazF.

For many years, we have been active as well in the field of structural glycobiology. With the tools of X-ray crystallography and calorimetry, our group investigated structure-function relationships of plant and bacterial lectins. Our crystal structure of LecB from P. aeruginosa has been the basis to design high affinity multivalent glycopeptide dendrimers that inhibit biofilm formation. The crystal structure of the Pseudomonas bacteriocin LlpA  has revealed a tandem of two monocot mannose binding lectin (MMBL) domains, of which one is active against high mannose oligosaccharides.