Genetic determination of the meso-diaminopimelate biosynthetic pathway of mycobacteria

J. D. Cirillo, T. R. Weisbrod, A. Banerjee, B. R. Bloom, W. R. Jacobs

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The increasing incidence of multiple-drug-resistant mycobacterial infections indicates that the development of new methods for treatment of mycobacterial diseases should be a high priority. meso-Diaminopimelic acid (DAP), a key component of a highly immunogenic subunit of the mycobacterial peptidoglycan layer, has been implicated as a potential virulence factor. The mycobacterial DAP biosynthetic pathway could serve as a target for design of new antimycobacterial agents as well as the construction of in vivo selection systems. We have isolated the asd, dapA, dapB, dapD, and dapE genes involved in the DAP biosynthetic pathway of Mycobacterium bovis BCG. These genes were isolated by complementation of Escherichia coli mutations with an expression library of BCG DNA. Our analysis of these genes suggests that BCG may use more than one pathway for biosynthesis of DAP. The nucleotide sequence of the BCG dapB gene was determined. The activity of the product of this gene in Escherichia coli provided evidence that the gene may encode a novel bifunctional dihydrodipicolinate reductase and DAP dehydrogenase.

Original languageEnglish (US)
Pages (from-to)4424-4429
Number of pages6
JournalJournal of Bacteriology
Volume176
Issue number14
DOIs
StatePublished - Jan 1 1994

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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