Biosynthesis and Scavenging of Purines by Pathogenic Mycobacteria Including Mycobacterium leprae

SUMMARY: Purine biosynthesis de novo could not be detected in suspensions of Mycobacterium leprae isolated from armadillo tissue. In contrast, non-growing suspensions of other pathogenic mycobacteria, also isolated from infected host tissue did synthesize purines. Rates of synthesis, judged by incorporation of [2-14C]glycine or [3-14C]serine into nucleic acid purines were 600 times higher in M. microli and 110 times higher in M. avium - both isolated from infected mouse tissue - than the lowest possible rate detectable and therefore the highest possible rate in M. leprae. The rate of purine synthesis relative to purine scavenging (judged by comparing incorporation of [3-14C]serine and [8-14C]hypoxanthine into nucleic acid purines in suspensions of mycobacteria) varied only slightly – 4-fold in M. microti and 6-fold in M. avium- whether organisms were harvested from media with or without purines, from media with a low nitrogen content but containing a purine, from mice or even with starved organisms. Thus, the failure of M. leprae to synthesize purines could not be explained as either a result of using non-growing mycobacteria in the incubations with 14C-labelled precursors or as repression or inhibition of synthesis de novo. It appears that M, leprae requires a supply of the purine ring from its environment. Nucleotides, which may be the major source of the purine ring in the intracellular environment, were not taken up directly by M. leprae but could be hydrolysed first to nucleosides and then taken up.