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Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Speaker Abstracts
35
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.