New mechanism for complement killing of Gram-negative bacteria

The complement system plays a strategic role in the vertebrate immune system in protecting the host from infection by numerous pathogenic agents. The system consists of at least 30 proteins that orchestrate attack on pathogenic agents. Although the susceptibility of Gram-negative bacteria to complement attack has been under investigation for over 100 years, the mechanism(s) by which the complement directly kills Gram-negative bacteria (Escherichia coli J5) is not understood. Inner membrane damage to E. coli J5 by complement with the subsequent release of cytoplasmic and periplasmic markers are important for killing. That observation has been extended to show that complement attack on Gram-negative bacteria prevents the detoxification of methylglyoxal, a lethal by-product of glucose metabolism. It is very important to know that lysozyme is not required for killing by C5b-9 complexes. That is, C5b-9 complexes kill bacteria but lysis of the organisms do not occur in lysozyme depleted or lysozyme neutralized serum. Killing is a function of damage or injury to the cytoplasmic membrane in E. coli J5 by C5b-9 complexes with the subsequent accumulation of a toxic by-product (methylgloxal) from glucose metabolism.   Key words: Complement proteins, Gram-negative bacteria, cytoplasmic membrane, methylglyoxal.