RESUMO
The inhibitory effect of cationic proteins from rabbit polymorphonuclear leucocytes on the oxidation of NADH by staphylococcal membrane preparations is described. Both cyanide and haematin are shown to interfere with the inhibitory process, by different mechanisms. Other authors have shown that glucose repressed staphylococci are diverted to a fermentative mode of metabolism. These findings were confirmed by demonstrating that membrane preparations from staphylococci grown in the presence of glucose have diminished cytochrome and succinic dehydrogenase levels. From a comparison of the effect of the cationic proteins on NADH oxidation in membrane preparations from organisms grown normally and under conditions of glucose repression, and from knowledge of the different susceptibility to the cationic proteins of the two types of organisms, it is suggested that the cationic proteins exert their bactericidal action on staphylococci following an energy dependent binding to the membrane.
Assuntos
Proteínas Sanguíneas/farmacologia , Neutrófilos , Membrana Celular/análise , Membrana Celular/efeitos dos fármacos , Membrana Celular/enzimologia , Cianetos/farmacologia , Citocromos/análise , Heme/farmacologia , NADH NADPH Oxirredutases/análise , Neutrófilos/análise , Ligação Proteica , Staphylococcus aureus/efeitos dos fármacos , Succinato Desidrogenase/análise , Fatores de TempoRESUMO
Anaerobiosis, various respiratory inhibitors and certain agents altering cellular energetics profoundly affect the staphylocidal action of the cationic proteins from rabbit polymorphonuclear leucocytes. It is suggested that sensitivity to these proteins depends on the structure of the cell membrane as influenced by (1) the oxidation level of the cytochrome chain and (2) its energized state. Agents such as amytal and rotenone, which cause a block at the beginning of the chain and would increase its oxidation level, enhance killing, whereas those causing a block in or at the end of the chain, such a 2-n-heptyl-4-hydroxyquinoline-N-oxide, cyanide and anaerobiosis, which would cause reduction of a part or whole of the chain, prevent killing. Among agents altering the energized state of the membrane, dicyclohexyl-carbodi-imide, an ATPase inhibitor, does not prevent killing, whereas 2,4-dinitrophenol, carbonylcyanide-trifluoromethoxy-phenylhydrazone and 5-Cl, 3-t-butyl, 2'-Cl, 4'-NO2-salicylanilide, all uncouplers and ionophores for a specific ion, do prevent killing, although gramicidin, a relatively nonspecific ionophore, does not. The paper also contains an extension of previous work on the effect of iron and haematin, to include various other iron compounds and haematin derivatives.