William D. Nunn

Effects of Phosphonic Acid Analogues of Glycerol-3-Phosphate on the Growth of Escherichia coli: Phospholipid Metabolism

The effects of glycerol-3-phosphate, 3,4-dihydroxybutyl-1-phosphonate, and 2,3-dihydroxypropyl-1-phosphonate on the metabolism of Escherichia coli strains 8 and 1908 were determined. These strains lack the membrane-bound glycerol-3-phosphate dehydrogenase and are constitutive for the glycerol-3-phosphate transport system. Such cells were more sensitive to growth inhibition by the four-carbon phosphonate than by glycerol-3-phosphate. The three-carbon phosphonate did not appear to inhibit cell growth. The incorporation of labeled precursors of lipid, protein, ribonucleic acid, or deoxyribonucleic acid into bacterial cells was measured in the presence of either glycerol-3-phosphate or one of its phosphonic acid analogues. The phosphonic acid analogues inhibited the uptake of labeled acetate into the lipid fraction to the greatest extent. The incorporation of [33P]PO4 into phospholipids was strongly inhibited by 3,4-dihydroxybutyl-1-phosphonate but was only slightly affected by 2,3-dihydroxypropyl-1-phosphonate. Glycerol-3-phosphate inhibited the incorporation of labeled uracil to the greatest extent during the first 20 min; however, this effect was largely reversed after 90 min. Only 3,4-dihydroxybutyl-1-phosphonate altered the distribution of labeled acetate into the phospholipids of strain 8, decreasing the percentage of counts in the phosphatidylglycerol fraction. The three-carbon phosphonate probably alters acetate incorporation by affecting the acetyl-coenzyme A pool, whereas the 3,4-dihydroxybutyl-1-phosphonate has a definite effect upon phospholipid metabolism. It is suggested that l-glycerol-3-phosphate:cytidine monophosphate phosphatidyltransferase is the probable site of action.