This proposal concerns the role and regulation of defined phospholipases during phagocytosis by PMN and during the antibacterial action of potent membrane-active proteins present in inflammatory fluids or purified in this laboratory from polymorphonuclear leukocytes (PMN).
Our specific aims are to examine: (1) The molecular determinants of the action of selective phospholipases A2 (PLA2) (e.g. PMN, inflammatory fluid) against phospholipase A-less mutants of Escherichia coli and the structural basis of the functional diversity of this conserved family of 14 kDa PLA2; (2) The regulation of bacterial (phospho)lipid degradation during phagocytosis and its role in intracellular bacterial killing and disassembly; and (3) The nature and possible functional consequences of the interaction of extracellular PLA2 with PMN or other """"""""inflammatory"""""""" host cells.
These aims have their origin in our earlier work and their pursuit will therefore rest heavily on well-tested methods used in this laboratory, including: collection of PMN and inflammatory exudates; functional assays of PMN (protein)-bacteria interactions such as phagocytosis, bacterial killing, bacterial phospholipid degradation and biosynthesis; purification of proteins, including PLA2; construction and expression of recombinant PLA2 variants; and construction and use of bacterial mutants. The long-term objectives of this proposal concern two fundamental questions: (l) What regulates the action of defined endogenous and exogenous phospholipases on the phospholipids of natural membranes? (2) What determines the extent of digestion and disassembly of bacteria killed by phagocytes? The proposed studies are likely to provide new insights related to the function of host defenses in infection and of membranes in general.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI018571-14
Application #
2060729
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1985-09-01
Project End
1998-08-31
Budget Start
1995-09-01
Budget End
1996-08-31
Support Year
14
Fiscal Year
1995
Total Cost
Indirect Cost
Name
New York University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012
Weiss, Jerrold P (2015) Molecular determinants of bacterial sensitivity and resistance to mammalian Group IIA phospholipase A2. Biochim Biophys Acta 1848:3072-7
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