The phosphonic acid analog of phosphatidyglycerol phosphate: influence on Escherichia coli growth and physiology

Abstract

At 20 μM, rac-3,4-dihydroxybutyl-1-phosphonate (DBP) has only a slight bacteriostatic effect on Escherichia coli. However, cells lose viability when the medium also contains either 20 mM magnesium or calcium ions. Magnesium ions stimulate the incorporation of DBP into (1,2-diacyl)- sn-glycerol- d-4′-phosphoryloxy-3′-hydroxybutyl-1′-phosphonate, the phosphonate analog of phosphatidylglycerol phosphate. Much higher DBP cocnentrations are needed the growth of a pgsA3 mutant than to block the growth of an isogenic wild-type strain. The DBP-treated pgsA mutant also has a much higher survival rate when stored in the cold than does the DBP-treated wild-type strain. Furthermore, the pgsA3 mutant grows normally in the presence of DBP and magnesium ions. Treatment with DBP and magnesium ions does not appear to disrupt the cell's inner or outer membranes. However, it does block macromolecular and phosphoglyceride synthesis. A combination of 20 μM rac-DBP and 0.5 mM spermidine or 0.125 mM spermine is bacteriostatic. These studies indicate that the PGP analog contributes to DBP's bacteriostatic effect when the growth medium contains low concentrations of magnesium or calcium ions and is responsible for its bactericidal effect when the medium contains high concentrations of these ions.