Phages in feces : developing a platform for discovery of Enterococcus lysins

While broad-spectrum antibiotics are effective in treating acute bacterial infections, the detrimental effects of broad-spectrum antibiotics on the microbiome are becoming increasingly clear. Therefore, a current paradigm shift focuses on the elimination of the disease-causing bacteria while conserving and even restoring a healthy balance in the microbiome during the treatment of infections. Lysins are enzymes encoded by bacteriophages that degrade the peptidoglycan layer of the bacterial cell wall, resulting in osmotic lysis of the bacterial cell. Because lysins are specific to certain bacteria, they could play a role in meeting the need for new, narrow-spectrum antibiotics. The first lysins are currently tested in clinical trials, emphasizing their potential as a new class of antibiotics. However, certain hurdles need to be taken to make lysins applicable as an antibiotic treatment against a variety of bacterial infections. One of these hurdles is the establishment of a platform enabling a fast discovery of lysins targeting diverse bacteria. The aim of this research project is to adapt a platform for high-throughput discovery of lysins targeting Enterococcus in a representative gut environment. Because enterococci are natural inhabitants of the gut, feces will be used as start material. However, the platform will be adjustable to use diverse start materials and to target diverse bacteria as well. Therefore, such a generic platform could contribute to the establishment of lysins as a new, narrow-spectrum antibiotic class with a multitude of possible applications