Complement resistance is an important virulence factor in the pathogenesis of bacterial gram negative infections. A more complete understanding of its complement resistance determinants may lead to improved or novel modalities for therapeutic intervention as well as an insight as to the mechanism of complement's action.The experimental approach taken for this project involves transposon mutagenesis of the chromosome and plasmid(s) of a clinical isolate of Escherichia coli that is highly complement resistant. We are using a transposon system (TnphoA) designed to mutagenize and identify mutants in outer, periplasmic and cytoplasmic membrane proteins. Mutants are screened for an increased sensitivity to serum and the acquisition of this phenotype will presumably be the result of the disruption of genes that play a role in complement resistance.This method makes no assumptions as to what genes contribute to complement resistance and will hopefully identify previously unrecognized gene products that play a role in this process.
