Inhibition of bacterial growth by beta-chloro-D-alanine.

Abstract

The D- and L-isomers of beta-chloroalanine inhibit the growth of Diplococcus pneumoniae, Streptococcus pyogenes, Bacillus subtilis, and Escherichia coli. With pneumococcus the inhibition by beta-chloro-D-alanine is completely prevented by either D-alanine or D-alanyl-D-alanine, while L-alanine is not effective in preventing the inhibition. The inhibition of growth by beta-chloro-L-alanine is not affected by D-alanine and is only partially prevented by high concentrations of L-alanine. The intracellular free alanine in untreated E. coli and B. subtilis is about 95% in the D-configuration while the free intracellular alanine in both organisms after treatment with beta-chloro-D-alanine is predominantly the L-isomer. These results suggested that the beta-chloroamino acid inactivates alanine racemase (EC 5.1.1.1). Indeed, when extracts of E. coli or B. subtilis were treated with beta-chloro-D-alanine, the activities of alanine racemase and of D-glutamate-D-alanine transaminase were found to be 90-95% inhibited. Studies with mice have shown that beta-chloro-D-alanine is an effective antibacterial agent in vivo againt D. pneumoniae, S. pyogenes, and E. coli.