The Relation of the Tricarboxylic Acid Cycle to Bacterial Infection IV. The Effect of Three Metabolic Inhibitors and Salmonella Typhimurium on the Citric Acid Content of Mouse Tissues

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Abstract
Citric acid, assayed colorimetrically, accumulates in liver, kidney, spleen, heart, duodenum, and blood of mice following intraperitoneal injn. of each of 3 inhibitors (malonate, arsenite, fluoroacetate) in dosages known to reduce survival time of mice infected with Salmonella typhimurium. The degree of accumulation varies with tissue and with inhibitor. Significant increases in citric acid also occurred after injn. of a heat-killed suspension of S. typhimurium but not when killed cells of Aero-bacter aerogenes were injected. Mice injected with both malonate and killed cells of S. typhimurium accumulated more citric acid in heart and duodenum than animals injected with either substance alone. This summation of metabolic blockage may help to explain why mice injected with heat-killed S. typhimurium followed, after 15 hrs., with 6 hourly injns. of 20 mg. malonate, have a reduced survival time compared with mice given only antigen and an equal number of injns. of sterile saline.