Inhibition of Escherichia coli growth and diaminopimelic acid epimerase by 3-chlorodiaminopimelic acid

• DOI: 10.1128/aac.32.8.1119
• Publication Date: 2012-06-28T00:04:52Z
• Authors: R J Baumann; E H Bohme; J S Wiseman; M Vaal; J S Nichols
• Keywords: Auxotrophy; Diaminopimelic acid; Growth inhibition

The diaminopimelic acid (DAP) analog, 3-chloro-DAP, was synthesized and tested as the racemic for antibacterial activity inhibition of DAP epimerase. 3-Chloro-DAP a potent inhibitor epimerase purified from Escherichia coli (Ki = 200 nM), it is argued that 3-chloro-DAP converted to tight-binding transition state analog at active site this enzyme. Furthermore, inhibited growth two E. mutants. In one mutants known supersusceptibility beta-lactams, not seen until mid-log phase growth, while in other mutant, auxotroph, occurred much earlier. Growth reversed by both strains. reversal specific meso-DAP, indicating target 3-chloro-DAP. Thus we suggest novel mechanism bacterial which depends on analog.