Next generation antimicrobial polymers

• Applicant: Dr. Matthias Hartlieb
• Subject Area: Polymer Materials ; Biomaterials ; Preparatory and Physical Chemistry of Polymers
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 445804074

The development of antibiotics is one of the major milestones of our society and enabled the development of modern medicine. The rapid progression of multi-drug resistant pathogens is jeopardizing these achievements and has been labelled a "major threat to health and human development" by the world health organization. The steady decrease in new antibiotics in combination with a growing number of infections by multi-drug resistant bacteria leads humanity into the direction of a post-antibiotic era, endangering the advances of modern medicine.One way to counteract these developments is the use of membrane active substances for infection treatment, as they are highly unlikely to be affected by bacterial resistance. The natural prototypes for such systems are antimicrobial peptides, which are part of the innate immune system. However, these biomolecules suffer from their inherent degradability, limited selectivity between pathogenic and host cell, and possess immune-regulatory properties. To overcome these issues, researchers have developed polymeric mimics of antimicrobial peptides, which possess cationic as well as hydrophobic units able to disrupt cellular membranes. However, no ideal design strategy has been found so far, and their selectivity remains a major issue, limiting their suitability for e.g. clinical studies.This proposal aims at developing the next generation of antimicrobial polymers by mimicking properties of antimicrobial peptides that have not been considered so far. This involves the creation of bottle brush copolymers that consist of multiple antimicrobial building blocks. Covalent bottle brushes, as well as supramolecular fibers are to be developed and their multivalent display of membrane active sub-units is envisioned to increase their activity. In addition, the segmentation of functional subunits within those materials will be varied systematically as this parameter has been shown to be of paramount importance for their activity and selectivity. Furthermore, active targeting strategies will be developed to concentrate the activity of antimicrobial polymers at the site of the infection and, in addition, increase their selectivity for specific pathogens. Finally, combinatorial therapies of multiple different systems will be developed to reveal potential synergistic effects between the materials.The introduction of new features and concepts in antimicrobial polymers will boost their performance and will bring them closer to an application. Thus, by supplementing or even substituting conventional antimicrobial therapies, these systems will help to solve the issue of antimicrobial resistance.

• DFG Programme: Independent Junior Research Groups
• Major Instrumentation: Size Exclusion Chromatography system including RI, UV, and MALS detection
• Instrumentation Group: 1350 Flüssigkeits-Chromatographen (außer Aminosäureanalysatoren 317), Ionenaustauscher