For years, the news of multi-drug resistant tablets scared the doctors and patients. Methicillin-resistant streptococci (MRSAs) in particular grow in the problem in clinics and nursing homes. Only in 2015 there were approximately 670,000 EU infections caused by multi-drug resistant pathogens, which left 33,000 dead patients .
Active substance from nasal flora
This is reactivated by antibiotic research after years of stagnation. However, recently approved antibiotics fear that they will quickly become resistant to new antibiotics. Just enough to look at other active ingredients. Scientists from Tübingen have found what they are looking for: they managed to isolate the Lugdunin peptide from the nasal flora bacterium, Staphylococcus lugdunensis.
Transmembrane voltage is canceled
This peptide was further investigated by Tübingen scientists at the team from the University of Göttingen and the German Center for Infection Research and came up with an antibiotic mechanism of action that differs from classical antibiotics: for bacterial cells it is important that concentrations of electrically charged particles in the interior differentiate the cell and surrounding surroundings. Lugdunin is able to transport positively charged ions of hydrogen through the membrane and eliminates the difference in charge between the inside of the cell and the external cell. This leads to some sort of energy breakdown, the bacterial cell dies .
Research on preclinical resistance
So far all new antibiotics have become resistant. Therefore, before going into a clinical study, the team wanted to know how much the potency was to develop resistance. For this purpose, the research team has produced a large number of lugdunin derivatives, which they call fibropeptides. Gradually, they changed parts of the chemical structure and each determined antibiotic activity.
Structural mirror image tests
In addition, researchers have found that there is no difference in the effect of antibiotics between the original molecule and its mirror image. Therefore, it can be demonstrated that the efficacy of Lugdunin is not based on spatial interaction, which hinders the rapid development of resistance. Resistance to Lugdun could not be generated in laboratory tests .
The chemical structure of Lugdunin consists of rings of building blocks of amino acids (peptide structures) incorporating a characteristic ring-like compound of thiazolidine sulfur nitrogen. This thiazolidine ring is essential for the antibacterial effect. Since the structure of this ring looks like a jewelry clasp (lat. Fibula), researchers have given their new class of drugs called fibropeptides .
Clinical trials are required
Whether Lugdunin and related substances can be used effectively and safely in the future to treat infections with multi-drug resistant bacteria, researchers have, among other things, discovered in the context of the Tübingen Excellence cluster's "control of microorganisms in the fight against infections" cluster.