Studies were performed in three areas: 1) Mechanism of serum resistance in gram negative bacteria. We found that C3 deposition on a serum resistant Salmonella strain occurred only on the small subset of LPS molecules bearing the longest O-Polysaccharide (O-PS) side chains, due to steric blocking of short O-PS side chains from complement attack. The LPS topography on the bacterial surface required to sterically block C3 deposition and to confer serum resistance was identified. Experiments on the mechanism of serum resistance in cystic fibrosis isolates of Pseudomonas aeruginosa and in Campylobacter fetus demonstrated that these organisms had unique mechanisms of serum resistance. 2) Mechanism of bacterial killing by C5b-9. Experiments investigating release of periplasmic and cytoplasmic markers from E. coli J5 as the C9:C5b-8 ratio varied indicated that killing and release of the large periplasmic marker, beta-lactamase, and the small cytoplasmic marker, 86Rb, required multimeric C9 within C9. 3) Mechanism of action of bactericidal and blocking IgG for Neisseria gonorrhoeae (GC). Blocking IgG for GC competes with bactericidal IgG for binding, and leads to complement deposition at new sites on the outer membrane at which C5b-9 is not bactericidal. Bactericidal activity of monoclonal antibodies (Mab) to GC was also tested. A difference in the bactericidal activity of Mab to the major outer membrane (PI) of two strains bearing ostensibly identical PI's was due to minor amino acid differences in the surface exposed portion of the molecule. A Mab to the H8 antigen in GC, a recently described highly conserved antigen, was highly bactericidal for some but not all GC strains despite binding to the surface of all organisms.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Intramural Research (Z01)
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