The goal of this research is to understand how certain strains of Gram-negative bacteria are able to withstand the action of the membrane attack complex (MAC) of complement. However, the means by which a bacterial cell elude lysis are ambiguous because the molecular mechanisms that cause cell death as a result of the MAC deposition are not understood. A primary aim of this project is to define how the molecular composition of the MAC relates to the expression of the known membranolytic activity of the complex. Membrane damage to complement- sensitive and complement-resistant bacterial cells will be measured as a function of the molecular composition of the C5b-9 complex.
In Specific Aim 1, the principal investigator will compare the structure, activity, and fate of MAC and MAC precursor complexes on complement-sensitive and complement- resistant cells. 125I-labeled C8 will be used to assess the number of C5b-8 complexes per cell.