Cell extracts of Brucella abortus (British 19) catabolized erythritol through a series of phosphorylated intermediates to dihydroxyacetonephosphate and CO2. Cell extracts required adenosine 5'-triphosphate (ATP), nicotinamide adenine dinucleotide (NAD), Mg2+, inorganic orthophosphate, and reduced glutathione for activity. The first reaction in the pathway was the phosphorylation of mesoerythritol with an ATP-dependent kinase which formed D-erythritol 1-phosphate (D-erythro-tetritol 1-phosphate). D-Erythritol 1-phosphate was oxidized by an NAD-dependent dehydrogenase to D-erythrulose 1-phosphate (D-glycero-2tetrulose 1-phosphate). B. abortus was found to lack the succeeding enzyme in the pathway and was used to prepare substrate amounts of D-erythrulose 1-phosphate. D-Erythritol 1-phosphate dehydrogenase (D-erythro-tetritol 1-phosphate: NAD 2-oxidoreductase) is probably membrane bound. D-Erythrulose 1-phosphate was oxidized by an NAD-dependent dehydrogenase to 3-keto-Lerythrose 4-phosphate (L-glycero-3-tetrosulose 4-phosphate) which was further oxidized at C-1 by a membrane-bound dehydrogenase coupled to the electron transport system. Either oxygen or nitrate had to be present as a terminal electron acceptor for the oxidation of 3-keto-L-erythrose 4-phosphate to 3-keto-L-erythronate 4-phosphate (L-glycero-3-tetrulosonic acid 4-phosphate). The ,Bketo acid was decarboxylated by a soluble decarboxylase to dihydroxyacetonephosphate and CO2. Dihydroxyacetonephosphate was converted to pyruvic acid by the final enzymes of glycolysis. The apparent dependence on the electron transport system for erythritol catabolism appears to be unique in Brucella and may play an important role in coupling metabolism to active transport and generation of ATP.Smith and co-workers (20, 33, 37) first described the unique role of erythritol in the pathogenesis and physiology of the genus Brucella. Extensive growth of Brucella occurs in fetal tissues and fluids of pregnant cows, sheep, goats, and sows, leading to endotoxin shock and abortion. In contrast to domestic animals, the bacteria cause a chronic disease in man in which cells of the reticuloendothelial system are parasitized. It is significant that erythritol is present only in fetal fluids and tissues of animals which suffer acute infectious abortions; however, considerable controversy has been raised concerning possible relationship(s) between erythritol utilization and virulence (23,24). Infections with B. melitensis and B. suis have been enhanced by co-injection of erythritol (20). Erythritol may play some selective role in tissue localization, since most maternal pathogens do not localize in fetal tissues. It is possible that, through the centuries of association with domestic animals, a unique enzyme system for erythritol catabolism has evolved which is important in the physiology of Brucella.Anderson and Smith (1) reported that B. abortus preferentially utilized erythritol in a complex medium containing high concentrations of D-glucose and amino acids. The 4-carbon polyol serve...