GENETIC DETERMINATION OF THE MESO-DIAMINOPIMELATE BIOSYNTHETIC-PATHWAY OF MYCOBACTERIA

The increasing incidence of multiple-drug-resistant mycobacterial infe ctions 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 myc obacterial peptidoglycan layer, has been implicated as a potential vir ulence 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, d apA, dapB, dapD, and dapE genes involved in the DAP biosynthetic pathw ay of Mycobacterium bovis BCG. These genes were isolated by complement ation of Escherichia coli mutations with an expression library of BCG DNA. Our analysis of these genes suggests that BCG may use more than o ne 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 b ifunctional dihydrodipicolinate reductase and DAP dehydrogenase.