Advanced Trojan Horse

The rising amount of microbial resistances urge for innovation and new therapeutics. Many substances already available in the lab are potent as antibiotics but cannot be used in humans due to toxicity or problems in delivery. Therefore, we used aminocoumarins and created a new derivative via a semi-biosynthetic synthesis approach. The introduction of specific modifications changes the pattern of interaction with proteins while also improving the chemical properties of aminocoumarins. Our modification specifically targets ß-lactam resistant pathogens. For proof of principle, we developed a suitable test system consisting of an E.coli-based pathogen model and a toxicity assay. Additionally, we performed an in silico prediction of changes in binding affinity to target proteins. In conclusion, we created an antibiotic that is only activated by ß-lactam resistant pathogens itself via enzymatic cleavage while not affecting other cells in the human body - the advanced Trojan horse is set free.

More information on http://2017.igem.org/Team:Tuebingen

Marcel Condrady, Hannah Brasse, Madeleine Heep, Mirjam Gneiting, Vic-Fabienne Schumann, Milena Krach, Antonia Graul, Michael Krummhaar, Brian Weidensee, Nikolas Layer