Induction of complement sensitivity in Escherichia coli by citric acid andlow pH

Aims: The lytic functions of the complement system play an important role i n the control of Gram-negative infections. Complement-resistant Escherichia coli LP1395 (O18) grown under normal conditions can survive the bactericid al action of complement present in human serum. Towards elucidating the mec hanisms of complement resistance, the resistance of E. coli LP1395 grown un der conditions of low pH and in the presence of citric acid was tested. Methods and Results: E. coli LP1395 becomes sensitive to complement after g rowth in the presence of citric acid at pH 5. Complement resistance could b e restored when the cells were transferred to pH 7 media. However, this rec overy was greatly impaired when the cells were transferred to pH 7 media wi th chloramphenicol. This implies that protein synthesis may be involved in complement resistance. The cells exposed to citric acid at pH 5 showed no i ndication of a generalized outer membrane (OM) permeability when compared w ith those grown under normal conditions in terms of sensitivity to lysozyme , uptake of lipophilic dye, or sensitivity to a number of antibiotics. Conclusions: Complement-resistant LP1395 may acquire a sensitivity to compl ement due not to a generalized disruption of the OM barrier, but possibly t o the alteration of the activity of one or more normal complement resistanc e factors. Significance and Impact of the Study: The elucidation of the mechanisms of complement resistance of Gram-negative pathogens would bring important info rmation about bacterial infections. Complement resistance factors could als o be potential targets in antimicrobial therapies.