This proposal concerns the determinants and biological role of the bacterial phospholipid degradation that accompanies the bactericidal action of polymorphonuclear leukocytes (PMN) and of potent membrane-active bactericidal proteins that recently have been purified in this laboratory.
Our specific aims are to examine: I. The factors that determine differences among phospholipases A2 in their ability to hydrolyze the phospholipids of E.coli S17 (a phospholipase A-less mutant) in the presence of bactericidal concentrations of these purified membrane-active proteins. II. The determinants of bacterial phospholipid degradation during phagocytosis by PMN. III. The role of the respiratory burst in digestion of bacteria killed by PMN.
These aims have their origin in our earlier work and their pursuit will therefore rely heavily on well-tested methods used in this laboratory, including: assays for measuring the interaction of PMN with bacteria; use of bacterial mutants; assays for lipid biosynthetic and degradative activities; purification of proteins; chemical modification of proteins. Our long-term objectives, which relate to membrane biology and host-defense against infection, are to explore: 1) what regulates the action of defined intrinsic and exogenous phospholipases on the phospholipids of natural membranes. 2) the host's ability to digest microbial invaders and the reasons and pathophysiological consequences of incomplete digestion.
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