Myeloperoxidase, hydrogen peroxide, chloride antimicrobial system: nitrogen-chlorine derivatives of bacterial components in bactericidal action against Escherichia coli.
In the presence of Escherichia coli, myeloperoxidase-catalyzed oxidation of chloride ion resulted in formation of long-lived chloramine and/or chloramide derivatives of bacterial components. The same amount of these nitrogen-chlorine (N-Cl) derivatives was obtained with either hypochlorous acid (HOCl) or the myeloperoxidase system, indicating that myeloperoxidase catalyzed the oxidation of chloride to HOCl. Identical killing was obtained with HOCl or the myeloperoxidase system. About 30 to 50% of the oxidizing equivalents of HOCl were detected as N-Cl derivatives of peptides or peptide fragments that were released from the bacteria. The apparent molecular weight distribution of the peptides decreased with increasing amounts of HOCl, suggesting that peptides were fragmented by oxidative cleavage of chloramide derivatives of peptide bonds. The remaining 50 to 70% of the oxidizing equivalents of HOCl were rapidly consumed in peptide bond cleavage or the oxidation of other bacterial components. There was a close correspondence between the oxidation of bacterial sulfhydryls and bactericidal action. The N-Cl derivatives were lost and the oxidation of bacterial sulfhydryls increased over a period of several h at 37 degrees C. These changes were accompanied by increased killing. The increase in sulfhydryl oxidation and killing could be prevented by washing the bacteria to remove the N-Cl derivatives. Therefore, the N-Cl derivatives could oxidize bacterial components long after the myeloperoxidase-catalyzed oxidation of chloride was complete.
D002700:Chloramines / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism* / Q000494:pharmacology; D010544:Peroxidases / Q000378:metabolism*
D002700:Chloramines; D002712:Chlorides; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D010544:Peroxidases; D009195:Peroxidase