Studies on the Metabolism of the Filarial Worm, Litomosoides carinii.

The filarial worm, Litomosoides carinii, has a high rate of aerobic and anaerobic glucose metabolism. Aerobically 30 to 45 per cent of the glucose utilized was converted to lactic acid, 25 to 35 per cent to acetic acid, and 10 to 20 per cent to a polysaccharide. Anaerobically over 80 per cent of the total carbohydrate removed by the filariae was metabolized to lactic acid, the remainder was accounted for by the production of acetic acid. The high rates of aerobic and anaerobic lactic acid production and of aerobic polysaccharide synthesis, as well as the absence of a postanaerobic increase of the oxygen uptake, differentiate the filarial worm, L. carinii, from the known metabolic characteristics of all other helminths and of most other invertebrates. The rate of aerobic lactate and pyruvate utilization by the filariae appears to be much slower than that of glucose. Anaerobically, dismutation of two moles of pyruvate to one mole of lactate, one mole of acetate, and one mole of CO(2), occurred. Aerobically, acetate production from pyruvate exceeded that of lactate. A significant proportion of the pyruvate metabolized aerobically by the filariae was not oxidized to acetate. In the presence of fluoroacetate, aerobic incubation of the filariae in a glucose-containing medium produced a marked decrease in the respiration of the organisms, an accumulation of pyruvate, a decreased formation of acetate, and an increase in aerobic glycolysis. Low concentrations of fluoroacetate (1 x 10(-3)M) inhibited the oxidative metabolism of pyruvate which did not result in the conversion of pyruvate to acetate; higher concentrations of this inhibitor produced also a decreased oxidation of pyruvate to acetate. No evidence has been obtained that fluoroacetate inhibits the respiration of the filariae because of a competitive inhibition of acetate oxidation. Respiration and glycolysis of filariae were markedly decreased by low concentrations of p-chloromercuric benzoate. This inhibition could not be reversed by a large excess of thioglycollate, cystein, glutathione, or H(2)S. Respiration of the filariae was completely inhibited by cyanide (2 x 10(-4)M). The cyanine dyes, a group of compounds possessing high chemotherapeutic activity in filariasis of the cotton rat, inhibited in low concentrations (6.5 x 10(-8)M) the oxygen uptake of the filarial worms. This decrease in oxidative metabolism was associated with a compensatory increase in aerobic glycolysis of the worms and with decreased rates of acetate production and of polysaccharide synthesis. The same metabolic changes were observed in filariae removed from cotton rats to which subcurative doses of a cyanine dye had been administered. Concentrations of cyanine dyes which produced an almost complete inhibition of filarial respiration had no effect on the rate of anaerobic glycolysis of the worms nor on the activity of cytochrome C or of cytochrome oxidase. It is concluded that, in contrast to many other parasitic invertebrates, oxidative metabolism is essential for the survival of the filarial worm, L. carinii, and that the chemotherapeutic activity of the cyanine dyes in filariasis of the cotton rat is due to the inhibitory effect of this group of compounds on the respiratory metabolism of the parasite.