Comparative toxicities of putative phagocyte-generated oxidizing radicals toward a bacterium (Escherichia coli) and a yeast (Saccharomyces cerevisiae)

Toxicities of the radiolytically generated oxidizing radicals HO center dot, CO3 center dot-, and NO2 center dot toward suspension cultures of a bacterium (Escherichia coli) and a yeast (Saccharomyces cerevisiae) were examined. As demonstrated by the absence of protection from the membrane-impermeable HO center dot scavenger polyethylene glycol (PEG), externally generated HO center dot was not bactericidal under these conditions; however, partial protection by PEG was observed for S. cerevisiae, indicating the presence of a fungicidal pathway involving external HO center dot. For both organisms, conversion of external HO center dot to the secondary radical, CO3 center dot-, by reaction with HCO3- increases their susceptibility to radiolytic killing. In contrast, externally generated NO2 center dot exhibited toxicity comparable to that of CO3 center dot- toward E. coli, but completely blocked the extracellular toxicity of HO center dot toward S. cerevisiae. Cogeneration of equal fluxes of NO2 center dot- and either HO center dot or CO3 center dot- also essentially eliminated the extracellular microbicidal reactions. This behavior is consistent with expectations based upon relative rates of radical-radical self-coupling and cross-coupling reactions. The different patterns of toxicity observed imply fundamentally different microbicidal mechanisms for the two organisms, wherein the bacterium is susceptible to killing by oxidation of highly reactive targets on its cellular envelope but, despite undergoing similar oxidative insult, the fungus is not. (c) 2006 Elsevier Inc. All rights reserved.