Molecular Mode of Antibiotic Action of Defensins and Related Innate Immunity Peptides

• Applicant: Professor Dr. Hans-Georg Sahl
• Subject Area: Immunology
• Term: from 2002 to 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5357590

Antibiotic peptides are important effector molecules in host-parasite interactions throughout the living world. In vertebrates, they function in first line host defense by antagonizing a wide range of microbes including bacteria, fungi and enveloped viruses. The antibiotic activity is thought to be based on their cationic amphipathic nature which enables the peptides to impair vital membrane functions. Molecular details for such activities have been elaborated with model membranes (pore formation models), however, there is growing concern that these models may not reflect the complex processes involved in the killing of microbes. Having studied the bacterial peptide antibiotic nisin, we have found that the overall killing activity of nisin is the result of several interdependent and independent activities such as the formation of target-mediated pores, inhibition of cell wall biosynthesis, formation of non-targeted pores and induction of autolysis. We propose to study the molecular modes of action of those antibiotic defense peptides which are found in humans (alpha- and beta- defensins, LL37 and histatins) and to investigate whether they primarily form pores, whether specific targets are involved in membrane poration and whether additional antibiotic activities may be found. Ultimately, we want to increase our knowledge on how the most ancient tools of host defense and the most abundant antibiotics in nature function and eventually learn from this project for the design of new generations of antibiotics.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1110: Innate Immunity