Stephan A. Sieber, Professor for Organic Chemistry at the Technical University of Munich (TUM) has been awarded the 2020 Future Insight Prize for his research on the development of new strategies against multidrug-resistant germs. The award, which includes a cash prize of one million euros, is sponsored by the science and technology company Merck.
The discovery of antibiotics has saved millions of human lives. However, in the meantime more and more bacteria have developed resistances to conventional antibiotics. Accordingly research by Stephan A. Sieber, TUM Professor for Organic Chemistry, centers on the development of strategies against this kind of resistant bacteria.
One of Stephan Sieber’s central strategies is to look for new potential targets within the bacterial metabolism. Working together with his team he identifies the proteins which are essential to the bacteria’s survival. If one of these proteins could be deactivated, it would be possible to starve the bacteria to death.
Another strategy is to prevent the ability of dangerous bacteria to produce toxins. The bacteria would then simply be "disarmed". Since this process does not kill the bacteria, the strategy also avoids the development of resistances.
"Another highly promising strategy is to take medications that have already been approved and test them for possible efficacy against bacteria. Here we focus on a class of human proteins referred to as kinases for which there are already a very large number of inhibitors," says Stephan Sieber.
In this context they have been successful with the active ingredient PK 150, a modification of the cancer medication Sorafenib. It attacks methicillin-resistant staphylococcus aureus (MRSA) germs in two ways at once: It impedes the bacterial energy metabolism while at the same time rupturing the cell walls.
"The fact that PK 150 addresses two different mechanisms in the cell at the same time makes it very difficult for the bacteria to develop resistances," says Stephan Sieber. "The probability that two mutations will take place in the same cell at exactly the right places is much lower."
The Merck Future Insight Prize promotes outstanding scientific and technological research activities for groundbreaking innovations in the fields Health, Nutrition and Energy. It comes with a 1 million euro cash award.
Stephan Sieber plans to invest the prize money in further development of the active ingredient PK 150. Initial preclinical studies are already in progress. "This support will now let us investigate the efficacy of PK 150 against other types of bacteria as well, for example mycobacteria or dangerous Gram-negative bacteria."