In this project, the scientists develop genetically engineered phage lysins and specific bacteriocins for the elimination of hospital germs such as Staphylococcus aureus, they clarify mechanisms of potential resistance mechanisms, and they analyse whether broad-spectrum or specifically acting agents have a more effective and lasting effect on colonization by S. aureus in the nasal cavity. The aim of the project is to identify new drugs for the prevention and treatment of staphylococcal infections and to further develop them in preclinical and clinical studies.
The general use of broad-spectrum antibiotics on our microbiome involves high risks: resistances development, other unwanted pathogens can proliferate or the same pathogen can take its place again more quickly. Highly selective and at the same time efficient strategies for elimination are urgently needed. Bactericidal proteins derived from bacteriophages are being investigated as an alternative strategy. They combine very fast-acting bactericidal activity, stability and activity in different environments with a high selectivity for specific bacterial species.
Another interesting class of substances are bacteriocins, which are highly active against S. aureus in the nasal cavity. Bacteriocins are toxins produced by competing bacterial strains and inhibit the growth of other strains of the same or similar bacterial species. Their advantage: Normally their activity spectrum is narrow and optimised to remove S. aureus from the human body surface. Specific "probiotic" bacterial strains could lead to new, highly efficient disposal strategies that could circumvent the increasing resistance to mupirocin and protracted treatment. Mupirocin is used today to combat colonisation with certain resistant pathogens in the nasal cavity.
In addition, new active substances produced by nasal bacteria with pronounced activity against S. aureus were discovered. These new antimicrobial peptides combine a narrow activity spectrum with a strong bactericidal activity and a low tendency to trigger spontaneous resistances. Moreover, patients who had this connection in the nasal cavity showed a six-fold lower risk of colonisation with S. aureus compared to patients in whom this bactericidal substance could not be detected.
The aim of the project is to find new active substances for the prevention and treatment of staphylococcal infections. These will be further developed in preclinical and clinical studies.