These studies are aimed at elucidation of 1) The pathway of biosynthesis of lipid A in Salmonella typhimurium; and 2) the molecular mechanisms of intermembrane translocation of lipopolysaccharide and phospholipid between inner and outer membrane. Genetic and biochemical approaches will be employed to analyze the pathway of lipid A synthesis. Conditional mutants in the pathway will be isolated, mapped and characterized biochemically with respect to the nature of mutant lipid A-related products formed and enzymatic reactions involved. Studies on translocation are aimed at identification of possible intermediate steps in lippopolysaccharide translocation - defective mutants and investigation of the relation of membrane topology to translocation of phospholipid.