Studies on the effect of various Cd'+ concentrations on substrate oxidation by whole cells of cadmiumsensitive Staphylococcus aureus 178 10s showed that oxidation of glutamate or pyruvate was highly sensitive to low Cd'+ concentrations (5 VM), whereas L-lactate oxidation was insensitive even to high Cd'+ concentrations (100 p ~) .
Location of the cadmium-sensitive targets in the enzyme systems involved in oxidation of these substrates was studied in subcellular fractions prepared from cells pretreated with 5 or 100 FM Cd'+. Activities of the cytoplasmic 2-oxoglutarate dehydrogenase complex (ODHC)') and pyruvate dehydrogenase complex (PDHC) were strongly inhibited with 5 p~ Cd", while with 100 p~ Cd" the inhibition was almost complete. In contrast, activities of the cytoplasmic NAD-dependent glutamate dehydrogenase (NAD-GDH), the membrane-bound NADH dehydrogenase (NDH) and HQNO-sensitive NADH oxidase were not sensitive to 100 p~ Cd". These data indicate that the accessible, cadmium-sensitive targets are located only in the cytoplasmic ODHC and PDHC. It is postulated that two vicinal dithiols present in ODHC and PDHC may be regarded as the primary cadmium-sensitive targets in the systems oxidizing glutamate or pyruvate. Since activities of the membrane-bound NAD-independent L-lactate dehydrogenase (iLDH) and HQNO-sensitive L-lactate oxidase were not affected by 100 p~ Cd", this indicates that the L-lactate oxidizing system lacks the accessible, cadmium-sensitive targets. The mechanism of Cd'+ toxicity to energy conservation with glutamate, pyruvate or L-lactate in S. aureus is discussed.