Regulation and role of phospholipases in host-bacteria interaction.
Deacylating phospholipases play essential roles in numerous biological events, requiring tight control of hydrolytic activity. Most cells, unless stimulated or perturbed, exhibit little phospholipid turnover. Activation of phospholipases A (PLA) is usually triggered by membrane perturbing conditions or agents. Some activators indiscriminately activate any PLA, others are highly specific. Our studies concern an activator that is a potent bactericidal protein with membrane-perturbing properties, isolated from polymorphonuclear leukocytes (PMN), that is only cytotoxic for gram-negative bacteria and primarily responsible for the fate of several gram-negative bacterial species, ingested and killed by the PMN. It is this protein that activates the hydrolysis of the phospholipids of the killed bacteria (E. coli) by three PLA: 1) an E. coli PLA, the pldA gene product; 2) a PLA2 of PMN; 3) a soluble PLA2 in the extracellular fluid of an inflammatory exudate. However, this activator protein does not trigger the action of many other PLA2, all members of a highly conserved class of PLA. Our structural studies (including genetic engineering) of both responsive and non-responsive PLA2 have revealed that the amino acid composition and sequence of the NH2-terminal alpha-helix of the PLA2 molecule are major determinants of the ability of the PMN protein to activate a given PLA2. Our results provide another demonstration that these important enzymes have diverged during evolution to perform different biological functions.
Department of Medicine, New York University School of Medicine, N.Y.
P
P
Elsbach
J
J
Weiss
G
G
Wright
S
S
Forst
C J
CJ
van den Bergh
H M
HM
Verheij
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D018407:Bacterial Physiological Phenomena; D001770:Blood Bactericidal Activity / Q000502:physiology; D001798:Blood Proteins / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins; D009504:Neutrophils / Q000201:enzymology* / Q000382:microbiology / Q000502:physiology; D010740:Phospholipases / Q000502:physiology*; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D008565:Membrane Proteins; C021623:bactericidal permeability increasing protein; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2