Bacterial cell wall digests itself
The foundations for this innovation were laid in the laboratories at TUM. “It was pure basic research to begin with,” emphasizes Sieber. “We tested hundreds of different agents in cultures with Staphylococcus aureus and came across a molecule that kills the bacteria off very effectively. We then examined the mode of action of this molecule, which we call PK150.” The results showed that PK150 has a fundamentally different mode of action to conventional antibiotics. Instead of suppressing biochemical processes, PK150 stimulates the excretion of proteins in the cell wall. Key enzymes are discharged from the cells and, in effect, the cell walls begin to digest themselves. At the same time, the molecule blocks the metabolic system, which means the cell cannot store any more energy and dies. Due to this dual mode of action, it is exceptionally unlikely that bacteria will develop mutations with resistances to this agent.
“Once it became clear that this molecule is a promising candidate for the development of a new antibiotic, we both knew we wanted to develop the agent,” recalls Sieber. “It is suitable for combating Staphylococcus aureus and other multidrug-resistant bacteria that are gram-positive, which means they have a single layer cell wall.” TUM applied for a patent for the structure of the optimized molecule for the first time in 2017 while Sieber and Macsics began the search for investors. Even during the coronavirus pandemic, the two researchers secured the support of the Boehringer Ingelheim Venture Fund following a virtual pitch.