Pyrimidine scavenging by Mycobacterium leprae

Abstract

Mycobacterium leprae incorporated exogenously supplied pyrimidenes as bases or nucleosides, but not as a nucleotide, into its nucleic acids. Notably, thymine was incorporated ∼5 times more rapidly than thymidine by bith suspensions of, or intracellular M. leprae. Thymine incorporation was significantly inhibited by clofazamine and dapsone at near‐pharmacological levels. Therefore, incorporation of thymine is preferable as an activity for assessing viability of M. leprae. Nucleosides were converted to nucleotides through kinases, bases through phosphoribosyltransferases. Alternatively, thymine and uracil could first be converted to nucleosides. Cytosine and uracil bases were interconvertable, and uracil alone could supply all the pyrimidine requirements of M. leprae, though conversion to the thymine base was extremely slow. Overall, pyrimidine scavenging occurs at a slower rate than, and appears not to be so important as purine scavenging in M. leprae.

The Rv1712 Locus from Mycobacterium tuberculosis H37Rv Codes for a Functional CMP Kinase That Preferentially Phosphorylates dCMP

“…It has been estimated that thymidine and uridine, for instance, may be available to mycobacteria growing in the host at a concentration range of 0.5 to 5.5 M (22). It was described that Myco- bacterium leprae, the causative agent of leprosy, is able to incorporate exogenously supplied pyrimidines as bases or nucleosides, but not as a nucleotide, into its nucleic acids (22). Besides M. leprae, it was reported that other pathogenic mycobacteria (such as Mycobacterium avium and Mycobacterium microti) cannot take up uridine nucleotides directly, but they are able to utilize the pyrimidines by hydrolyzing them to uridine and then taking up the latter (23).…”

Aspartate metabolism in Mycobacterium avium grown in host tissue an axenically and in Mycobacterium leprae

“…Furthermore, even though mycobacteria harvested from host tissue are subject to a lengthy purification procedure they appear to be metabolically intact : activities such as incorporation of hypoxanthine into nucleic acids are detected at levels similar to those found in axenically grown mycobacteria (Wheeler, 1987); the ATP content of M . leprae is comparable with the ATP content of rapidly growing mycobacteria (reviewed in Barclay 8z Wheeler, 1989); and in this study, uptake of lysine and methione -two of the aspartate family -was higher for host-grown M . avium than for axenically grown M .…”

“…Asparagine, glutamate, aspartate and various other amino acids and metabolic precursors and intermediates are available in host tissues in significant quantities and various micro-organisms, including mycobacteria, can accumulate these substances to concentrations many times higher than in the environment (see Holden, 1962;Sritharan et al, 1987) and thus could use them directly rather than having to synthesize them de novo. This certainly seems to be the case with mycobacteria growing in vivo, which can assimilate and utilize exogenous fatty acids (Wheeler & Ratledge, 1988) and nucleotides (Wheeler, 1987(Wheeler, , 1989) the key enzymes involved in the biosynthesis of these compounds being depressed simultaneously.…”