The inhibition of growth and cozymase synthesis in bacteria by halogen-substituted nicotinic acids

Abstract

The growth of Lactobacillus arabinosus, Staphylococcus aureus, Proteus vulgaris and Escherichia coli is inhibited by the 5 halogeno nicotinic acids in the following order of effectiveness: 5-fluoronicotinic acid > 5-chloronicotinic acid>5-bromonicotinic acid>2-and 6-fluoronicotinic acids. The inhibition is reversed competitively by nicotinic acid, nicotinamide and cozymase. The acceleration of glycolysis by nicotinic acid in washed suspensions of L. arabinosus and S. aureus is inhibited by 5-fluoronicotinic acid; acceleration by cozymase in L. arabinosus is not inhibited. 5-Fluoronicotinic acid caused similar effects on the acceleration of O2 uptake of P. vulgaris by nicotinic acid and its derivatives. Cozymase synthesis from nicotinic acid, nicotinamide, nicotinamide riboside, and to a lesser degree nicotinamide ribonucleotide, is inhibited by 5-fluoronicotinic acid in L. arabinosus. Cozymase uptake is not inhibited. A similar inhibition of synthesis of cozymase from nicotinic acid, nicotinamide and nicotinamide ribonucleotide was found in S. aureus. The inhibition is competitive when inhibitor and metabolite are added simultaneously, but non-competitive when inhibitor is added before metabolite. The magnitude of the inhibition of cozymase synthesis from nicotinic acid in L. arabinosus and S. aureus was increased at least 10-fold by prior incubation of the cells with the inhibitor. During the incubation the inhibitor was taken up and bound by the cells. The uptake of 5-fluoronicotinic acid is dependent on the presence of a concomitant glycolytic reaction. It is suggested that 5-fluoronicotinic acid inhibits several steps in the synthesis of cozymase, possibly by being metabolized along the synthetic route.