Investigation of the essentiality of glutamate racemase in Mycobacterium smegmatis

J Bacteriol. 2014 Dec;196(24):4239-44. doi: 10.1128/JB.02090-14. Epub 2014 Sep 22.

Abstract

The mycobacterial cell wall frequently has been used as a target for drug development, and d-glutamate, synthesized by glutamate racemase (MurI), is an important component of peptidoglycan. While the essentiality of the murI gene has been shown in several bacterial species, including Escherichia coli, Bacillus anthracis, and Streptococcus pneumoniae, studies in mycobacteria have not yet provided definitive results. This study aimed to determine whether murI is indeed essential and can serve as a possible target for structure-aided drug design. We have achieved this goal by creating a ΔmurI strain of Mycobacterium smegmatis, a close relative of Mycobacterium tuberculosis. The deletion of the murI gene in M. smegmatis could be achieved only in minimal medium supplemented with D-glutamate, demonstrating that MurI is essential for growth and that glutamate racemase is the only source of D-glutamate for peptidoglycan synthesis in M. smegmatis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Isomerases / genetics*
  • Amino Acid Isomerases / metabolism*
  • Cell Wall / metabolism
  • Culture Media / chemistry
  • Gene Deletion
  • Genes, Essential*
  • Glutamic Acid / metabolism
  • Mycobacterium smegmatis / enzymology*
  • Mycobacterium smegmatis / genetics
  • Mycobacterium smegmatis / growth & development*
  • Peptidoglycan / metabolism

Substances

  • Culture Media
  • Peptidoglycan
  • Glutamic Acid
  • Amino Acid Isomerases
  • glutamate racemase