The deposition of C5b-9 complexes and its precursors on E. coli J5 during complement activation enhances uptake and toxicities of gentamicin

• Published in: Immunological investigations 2008-01, Vol.37 (3), p.245-261
• Main Authors: Bloch, Earl F, Morrison, Kasey, McDonald-Pinkett, Shelly, Baskin, Sheena, Campbell, Stephanie, Peters, Sharla, Dillahunt, Sandra, Evans, Dia, Lucas, Shantelle, Macatangay, Aimee, Kanaan, Yasmine
• Format: Article
• Language: English
• Subjects: Colony Count, Microbial; Complement Activation; Complement C5b - immunology; Complement Membrane Attack Complex - immunology; Complement Membrane Attack Complex - metabolism; Complement Pathway, Classical - immunology; Complement System Proteins - immunology; Escherichia coli; Gentamicins - immunology; Gentamicins - metabolism; Gentamicins - pharmacology; Humans
• ISSN: 0882-0139; 1532-4311
• DOI: 10.1080/08820130801973682

The complement system provides the host with protection against pathogenic agents and in some cases can result in damage to host tissue. However, the exact mechanism of how complement kills gram-negative bacteria in lysozyme-neutralized and or lysozyme-depleted serum is still under active investigation. In previous studies, it has been demonstrated that inner membrane damage by the membrane attack complex contributes to depolarization and the subsequent collapse of the membrane potential. In these studies we have shown that the membrane attack complex and its precursors provide additional protective effect by the enhanced uptake of antibiotics in the death of E. coli J5. Specifically, the deposition of C5b fragments from C6 neutralized Pooled Normal Human Serum (PNHS) and C5b6 complexes from C7 neutralized PNHS on E. coli J5 contribute to antibiotic uptake and killing. Since C5b and C5b6 do not form pores, we suggest that disturbances and or cracks in the outer membrane by the deposited complexes accelerates uptake of the antibiotics and enhanced killing of E. coli J5 employed in these studies.