Metabolism of purine bases remains poorly understood in the pathogenic bacterium Mycobacterium tuberculosis and closely related, nonpathogenic Mycobacterium smegmatis (Msm). To gain insight into the purine metabolism in mycobacteria, we tested uptake of purine bases with a ΔpurF Msm mutant with an inactive purine de novo biosynthesis pathway and confirmed that hypoxanthine and guanine, but not xanthine, can serve as nucleotide precursors for recycling in the salvage pathway. Further, we focused on purine catabolism in wild-type (wt) Msm. We found that only xanthine and guanine could serve as a sole nitrogen source for wt Msm. These data confirm that Msm catabolism of purines is directed mainly via oxidative guanine to xanthine interconversion and not through metabolic conversion of hypoxanthine to xanthine. Our data represent the first experimental evidence confirming the use of 8-oxo-purines as a nitrogen source by Msm.

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Flemingovo n 2 16610 Prague 6 Czech Republic

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The mycobacterial guaB1 gene encodes a guanosine 5'-monophosphate reductase with a cystathionine-β-synthase domain

Hypoxanthine-Guanine Phosphoribosyltransferase Is Dispensable for Mycobacterium smegmatis Viability