Inhibition of bacterial growth by beta-chloro-D-alanine.
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.
D000409:Alanine / Q000494:pharmacology*; D000410:Alanine Transaminase / Q000037:antagonists & inhibitors; D000591:Amino Acid Isomerases / Q000037:antagonists & inhibitors; D001412:Bacillus subtilis / Q000187:drug effects / Q000201:enzymology; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D002713:Chlorine / Q000494:pharmacology; D003864:Depression, Chemical; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects; D015091:beta-Alanine / Q000031:analogs & derivatives
D015091:beta-Alanine; C006977:3-chloroalanine; D002713:Chlorine; D000410:Alanine Transaminase; D000591:Amino Acid Isomerases; D000409:Alanine