National Biomedical Electron Paramagnetic Resonance Center

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Jimmy B. Feix, PhD

Professor of Biophysics

Department of Biophysics
Medical College of Wisconsin
8701 Watertown Plank Road
Milwaukee, WI 53226-0509
Phone: 414-955-4037
Fax: 414-955-6512
jfeix@mcw.edu

 


PubMed Publications

 

Research Interests

  • Biological and biochemical characterization of antimicrobial peptides
  • EPR site-directed spin labeling
  • Structure and function of membrane proteins

Mechanisms of Antimicrobial Peptides: Membrane Interactions

Antibiotic resistance is an increasingly serious problem in the treatment of infectious disease. During the past two decades, a large number of peptides with potent antibacterial, antiviral, and antifungal properties have been identified from a wide range of both vertebrate and invertebrate species. These antimicrobial peptides (AMPs) are an important component of the "innate" arm of host resistance, serving as a first line of defense against infection. Despite being evolutionarily ancient, resistance to AMPs has only rarely been observed. Consequently, there is great interest in the development of these peptides for the treatment of drug-resistant infections.
 


 


 


Models of Transmembrane Channel Formation

(A) Peptide a-helices (cylinders) initially associate parallel to the membrane surface, either superficially (left) or embedded just below the aqueous interface. (B) Peptides continue to accumulate at or near the bilayer surface, disrupting lipid packing and causing membrane thinning. This step may or may not involve peptide-peptide aggregation. Once a critical peptide/lipid ratio is reached, peptides either (C) insert into the membrane as a barrel-stave type pore, or (D) induce the localized formation of toroidal pores.

Our laboratory is involved in elucidating the mechanisms by which AMPs disrupt bacterial membrane structure, determining the basis of AMP selectivity for microbial cells, and developing more effective antimicrobial peptides and peptidomimetics. Whereas classical antibiotics generally target cell wall synthesis, protein translation, or some other highly specific target, AMPs are believed to function by directly disrupting the microbial cell membrane. Peptides are prepared using either recombinant DNA methods or solid-phase chemical synthesis, and their interactions with model membranes (liposomes) and cells are characterized by a variety of physical techniques including circular dichroism, fluorescence, and EPR site-directed spin labeling (SDSL). Our fundamental hypothesis is that a more complete understanding of peptide structure and dynamic interactions with the membrane will allow the design and development of improved AMPs and related antibiotics for the treatment of infections by existing drug-resistant strains such as Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA).


Membrane Proteins I

Membrane Proteins II

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