Biophysical Society Thematic Meeting - November 16-20, 2015

Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Speaker Abstracts

Bacterial Infections at Atomic Resolution Wolf-Dieter Schubert . University of Pretoria, Pretoria 0002, South Africa.

Infecting a multicellular organism is not easy for a bacterium, faced by many physical barriers and a highly developed, multi-tiered immune system. Bacteria nevertheless succeed by producing and secreting dedicated proteins, or so-called virulence factors, that help them to manipulate the host processes to their advantage. We are interested in how virulence factors are designed to bind to host receptors and proteins to re-programme host responses and outcomes in their favour. For this purpose we generally analyse disease-related protein complexes in which one component is of bacterial origin and the other is the corresponding host target. We predominantly use macromolecular crystallography to investigate how bacteria infect humans and other mammals at the molecular and atomic level. In addition, we quantify the binding affinity to explain how the bacterial virulence factor is able to outcompete any physiological binding partners of the host factor. Organisms that we are currently working on include Mycobacterium tuberculosis, the causative agent of tuberculosis, enterotoxigenic Escherichia coli (ETEC) causing dysentery mostly in small children, Listeria monocytogenes, a food-borne pathogen leading to blood poisoning, meningitis and miscarriages of unborn babies, as well as Legionella pneumophila, the cause of Legionnaires’ disease. Our studies include structural analysis, biophysical investigation of protein-protein interactions of bacterial virulence factors with host proteins, as well as cell-based infection studies.

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