Apparent involvement of purines in the control of expression of Salmonella typhimurium pyr genes: analysis of a leaky guaB mutant resistant to pyrimidine analogs

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Abstract
A leaky guaB mutant of S. typhimurium LT-2 was obtained during a selection for mutants resistant to a combination of the 2 pyrimidine analogs, 5-fluorouracil and 5-fluorouridine. In the absence of exogenous guanine compounds, the growth rate of this mutant is limited by the endogenous supply of guanine nucleotides due to a defective IMP dehydrogenase. Under these conditions the GTP pool is about 20% of normal, the CTP pool is reduced to below 60%, and the UTP pool is slightly elevated. Simultaneously, levels of the pyrimidine biosynthetic enzymes are abnormal: aspartate transcarbamylase, orotate phosphoribosyltransferase and orotidylic acid decarboxylase levels are increased 4-, 11- and 3-fold, respectively. Levels of dihydroorotase and dihydroorotate dehydrogenase decrease to 10 and 20%, respectively. The pyrimidine metabolism of the guaB mutant is restored completely by addition of guanine (or xanthine) to the growth medium. Purine nucleotide involvement in the regulation of expression of the pyr genes of S. typhimurium is indicated.