Effect of Lethal Doses of Complement on the Functional Integrity of Target Enterobacteria

Abstract

Exposure of a wide variety of gram-negative bacteria to serum results in the activation of either the classical or alternative pathway of complement and the generation of macromolecular C5b-9 protein complexes. When formed on the surface of susceptible Escherichia coli (Bladen et al. 1966) or other gramnegative bacteria (Bladen et al. 1967; Swanson and Goldschneider 1969; Harriman et al. 1982), C5b-9 complexes form remarkably stable lesions embedded in the bacterial envelope where they behave essentially as integral membrane proteins (Joiner et al. 1983; Kroll et al. 1983). Complexes are formed from the fluid-phase proteins (C5b, C6, C7, C8, and C9) of the terminal complement membrane attack pathway by spontaneous association following enzymatic cleavage of C5 (Bhakdi 1980; Mayer 1981). Polymerization is accompanied by the appearance of terminal apolar regions on the cylindrical C5b-9 complex that facilitate insertion into hydrophobic domains of target membranes (Bhakdi and Tranum-Jensen 1978). There is a large body of evidence indicating that insertion of complexes into the bacterial envelope is directly responsible for initiating the sequence of events that results in the death of the target bacterial cell (Inoue et al. 1968 b; Schreiber et al. 1979; Joiner et al. 1982 a, b; Kroll et al. 1984). Conversely, serum-resistant strains appear to escape the potentially lethal action of complement because C5b-9 complexes fail to insert in a stable fashion into the target membrane (Joiner et al. 1982b; Kroll et al. 1983; Taylor and Kroll 1984).