Candidacidal activity of the neutrophil myeloperoxidase system can be protected from excess hydrogen peroxide by the presence of ammonium ion.
Excessive concentrations of hydrogen peroxide inhibit the neutrophil myeloperoxidase system, presumably by inactivating the hypochlorous acid produced by this system. Ammonium ion generated by neutrophils and other cells can react with hypochlorous acid to produce monochloramine, an oxidant with good microbicidal activity, but relative resistance to inactivation by other compounds. In an assay based on the oxidation of 5-thio-2-nitrobenzoic acid, hydrogen peroxide reacted more readily with sodium hypochlorite (used as a source of hypochlorous acid) than with monochloramine. Also, in this assay Candida albicans yeast inactivated the oxidant activity of hypochlorous acid more completely than they did that of monochloramine. The killing of Candida by sodium hypochlorite, as determined in a standard colony count microbicidal assay, was inhibited by equimolar and greater concentrations of hydrogen peroxide; killing of this organism by monochloramine was not affected by a tenfold excess concentration of hydrogen peroxide. In microbicidal assays using 4 mU of myeloperoxidase and optimal or excessive concentrations of hydrogen peroxide or glucose and glucose oxidase to generate hydrogen peroxide, the excessive concentrations inhibited killing of Candida, but not Staphylococcus aureus. The inhibition of Candida killing could be reversed by addition of ammonium ion to convert hypochlorous acid to monochloramine. These results indicate that for certain organisms such as C albicans, conversion of hypochlorous acid to monochloramine by reactions with ammonium ion may extend the range of hydrogen peroxide concentrations under which killing by the myeloperoxidase system can occur by protecting the necessary microbicidal oxidants from inactivation by excess hydrogen peroxide.
Beilke
M A
MA
Department of Medicine, Medical College of Wisconsin, Milwaukee.
Collins-Lech
C
C
Sohnle
P G
PG
D000641:Ammonia / Q000378:metabolism; D002176:Candida albicans / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007477:Ions; D009504:Neutrophils / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism* / Q000494:pharmacology
D007477:Ions; D000641:Ammonia; D006861:Hydrogen Peroxide; D009195:Peroxidase