Synergistic Effect of Pactamycin and Sparsomycin on Mycoplasma -Induced Lethal Toxicity of Mice

Abstract

Pactamycin and sparsomycin, antitumor drugs which act synergistically with endotoxins, also potentiate the lethal toxicity of mice by Mycoplasma fermentans, strain K10. Sparsomycin (50 ug/20 g mouse, injected intraperitoneally 1 h after various doses of M. fermentans) exerted a minimal degree of synergism with few extra deaths, but with prolonged appearance of nonlethal disease. Pactamycin (75 gg in the same protocol) increased susceptibility to Mycoplasma-induced lethal toxicity approximately 1,000-fold. The optimal response was noted when pactamycin was administered in the period between 6 h before and 3 h after the administration of 108 colony-forming units of viable mycoplasmas. Doses of 12.5, 25, or 50 jig increased severity of signs, but only 75 ug/mouse produced synergism of the lethal effect. Methylprednisolone partially negated the synergism when injected simultaneously with the pactamycin 1 h after the cells. The lethal synergistic effect occurred with four species of Mycoplasma in addition to M. fermentans.

Levels of lysosomal enzymes in tissues of mice infected with Mycoplasma fermentans

“…Mycoplasma. The origin of M. fermentans, strain K10, and methods of cultivation and enumeration have been described previously (7,9,10). Cultures were grown to peak log phase in 500to 1,000-ml lots and were collected by centrifugation at 12,000 x g for 20 min.…”

Cytotoxic effect of Mycoplasma fermentans on mouse thymocytes

“…It has been shown that antitumor compounds that inhibit deoxyribonucleic acid synthesis (e.g., actinomycin D, sparsomycin, and pactamycin) act synergistically with the K10 toxin in vivo (3,4). It would be desirable to also evaluate these compounds in vitro, using the thymocyte system described here.…”

Role of Gram-Negative Sepsis in Lethal Toxicity Induced by Mycoplasma

“…These responses included lethargy, anorexia, diar-rhea, matted eyes, thymic involution, hepatocellular necrosis, and accumulations of leukocytes in alvec1ar septae [1,2]. In addition, mice could be sensitized to lethal toxicity and endotoxic shock by actinomycin D [2] and other antitumor drugs (e.g., pactamycin [9,10]) that display synergism with endotoxins but not with exotoxins.…”