THE EFFECT OF SOME KREBS CYCLE INHIBITORS AND INTERMEDIATES ON SHIGELLA INFECTIONS IN MICE

Recent reports have indicated that injection of substances inhibitory to enzymes of the tricarboxylic acid cycle, or of intermediate products of this cycle, would decrease survival time of mice challenged with a variety of organisms. Groups of mice were inoculated rectally with Shigella flexneri 3 organisms and then injected parenterally with one of the following disodium malonate, sodium arsenite, trisodium citrate, disodium succinate. Control groups were given either organisms alone, tricarboxylic acid TCA cycle inhibitors or intermediates alone, or these compounds heat-killed organisms. Within 72 hours S. flexneri 3 organisms alone killed 4 5.0 of 80 mice. In combination with malonate they killed 15 75 of 20, with citrate 10 50 of 20, with succinate 8 40 of 20, and with arsenite, 8 40 of 20. There were no deaths among 80 mice inoculated with heat-killed organisms alone. Among those that received heatkilled organisms plus inhibitors or intermediate, 3 15 of 20 injected with malonate died, 6 30 of 20 with citrate, 0 of 20 with succinate, and 2 20 of 10 with arsenite. There was no evidence of diarrhea in surviving animals. Shigella were recovered less often from mice injected with malonate, citrate or succinate and more often from those that received arsenite than from controls inoculated with organisms alone. Author