Mechanism of staphylococcal resistance to non-oxidative antimicrobial action of neutrophils: importance of pH and ionic strength in determining the bactericidal action of cathepsin G.
The staphylococcalcidal action of highly purified, enzymically inactive human lysosomal cathepsin G was studied. The bactericidal action of cathepsin G was optimal at pH 7.5 and was inhibited by NaCl; concentrations greater than 0.15 M NaCl completely inhibited killing of Staphylococcus aureus. Under optimal conditions (pH, temperature and NaCl concentration) the ED50 (effective dose) of cathepsin G against S. aureus strain 8325-4 was about 3.1 micrograms ml-1. Polymeric teichoic acid may serve as a binding site for cathepsin G by promoting electrostatic interactions since a mutant lacking this surface component exhibited enhanced resistance to the lethal action of cathepsin G, compared to the teichoic-acid-positive parental strain. These results suggest that (i) the ability of cathepsin G to kill intraphagosomal staphylococci may be regulated in part by the ionic strength of the environment and the pH of the maturing phagolysosome, and (ii) that strategies which retard acidification of the developing phagolysosome would promote the staphylococcalcidal action of cathepsin G.
Shafer
W M
WM
Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322.
Onunka
V C
VC
D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007108:Immune Tolerance; D009504:Neutrophils / Q000276:immunology*; D012697:Serine Endopeptidases; D012965:Sodium Chloride / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism; D013682:Teichoic Acids / Q000378:metabolism
D013682:Teichoic Acids; D012965:Sodium Chloride; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G