Investigation of the Essentiality of Glutamate Racemase in Mycobacterium smegmatis

Abstract

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 Δ murI 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 .