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(*), CO(3)(-)(*), and NO(2)(*) 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(*) scavenger polyethylene glycol (PEG), externally generated HO(*) 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(*). For both organisms, conversion of external HO(*) to the secondary radical, CO(3)(-)(*), by reaction with HCO(3)(-) increases their susceptibility to radiolytic killing. In contrast, externally generated NO(2)(*) exhibited toxicity comparable to that of CO(3)(-)(*) toward E. coli, but completely blocked the extracellular toxicity of HO(*) toward S. cerevisiae. Cogeneration of equal fluxes of NO(2)(-)(*) and either HO(*) or CO(3)(-)(*) 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.
King
David A
DA
Department of Chemistry, Washington State University, Pullman, WA 99164-4630, USA.
Sheafor
Mark W
MW
Hurst
James K
JK
D000935:Antifungal Agents / Q000494:pharmacology; D002254:Carbonates / Q000737:chemistry; D004307:Dose-Response Relationship, Radiation; D004926:Escherichia coli / Q000378:metabolism*; D005609:Free Radicals; D005720:Gamma Rays; D017665:Hydroxyl Radical; D008956:Models, Chemical; D030421:Peroxynitrous Acid; D010587:Phagocytosis; D011092:Polyethylene Glycols / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
D000935:Antifungal Agents; D002254:Carbonates; D005609:Free Radicals; D026361:Reactive Nitrogen Species; D030421:Peroxynitrous Acid; D017665:Hydroxyl Radical; D011092:Polyethylene Glycols