Following a brief introduction of cellular response to stimulation comprising leukocyte activation, three major areas are discussed: (1) the neutrophil oxidase; (2) myeloperoxidase (MPO)-dependent oxidative microbicidal reactions; and (3) MPO-independent oxidative reactions. Topics included in section (A) are current views on the activation mechanism, redox composition, structural and topographic organization of the oxidase, and its respiratory products. In section (B), emphasis is placed on recent research on cidal mechanisms of HOCl, including the oxidative biochemistry of active chlorine compounds, identification of sites of lesions in bacteria, and attendant metabolic consequences. In section (C), we review the (bio)chemistry of H2O2 and .OH microbicidal reactions, with particular attention being given to addressing the controversial issue of probe methods to identify .OH radical and critical assessment of the recent proposal that MPO-independent killing arises from site-specific metal-catalyzed Fenton-type chemistry.

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The adenylate energy charges (EC) of Escherichia coli 25922, Pseudomonas aeruginosa 27853, and Streptococcus lactis 7962 rapidly fell in nutrient-rich media from values in excess of 0.9 to below 0.1 when the organisms were exposed to lethal levels of HOCl. The same cells maintained in energy-depleted states were incapable of attaining normal EC values necessary for biosynthesis and growth when challenged with nutrient energy sources after HOCl exposure. These changes correlated quantitatively with loss of replicative capabilities. Initial rates of transport of glucose, succinate, and various amino acids that act as respiratory substrates and the ATP hydrolase activity of the F1 complex from the ATP synthase of E. coli 25922 also declined in parallel with or preceded loss of viability. These results establish that cellular death is accompanied by complete disruption of bacterial ATP production by both oxidative and fermentative pathways as a consequence of inhibition of inner membrane bound systems responsible for these processes.

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