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. 1993 Aug;175(15):4652–4661. doi: 10.1128/jb.175.15.4652-4661.1993

Pyrimidine metabolism by intracellular Chlamydia psittaci.

G McClarty 1, B Qin 1
PMCID: PMC204916  PMID: 8335624

Abstract

Pyrimidine metabolism was studied in the obligate intracellular bacterium Chlamydia psittaci AA Mp in the wild type and a variety of mutant host cell lines with well-defined mutations affecting pyrimidine metabolism. C. psittaci AA Mp cannot synthesize pyrimidines de novo, as assessed by its inability to incorporate aspartic acid into nucleic acid pyrimidines. In addition, the parasite cannot take UTP, CTP, or dCTP from the host cell, nor can it salvage exogenously supplied uridine, cytidine, or deoxycytidine. The primary source of pyrimidine nucleotides is via the salvage of uracil by a uracil phosphoribosyltransferase. Uracil phosphoribosyltransferase activity was detected in crude extracts prepared from highly purified C. psittaci AA Mp reticulate bodies. The presence of CTP synthetase and ribonucleotide reductase is implicated from the incorporation of uracil into nucleic acid cytosine and deoxycytidine. Deoxyuridine was used by the parasite only after cleavage to uracil. C. psittaci AA Mp grew poorly in mutant host cell lines auxotrophic for thymidine. Furthermore, the parasite could not synthesize thymidine nucleotides de novo. C. psittaci AA Mp could take TTP directly from the host cell. In addition, the parasite could incorporate exogenous thymidine and thymine into DNA. Thymidine kinase activity and thymidine-cleaving activity were detected in C. psittaci AA Mp reticulate body extract. Thus, thymidine salvage was totally independent of other pyrimidine salvage.

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Selected References

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  1. Baum K. F., Berens R. L., Marr J. J., Harrington J. A., Spector T. Purine deoxynucleoside salvage in Giardia lamblia. J Biol Chem. 1989 Dec 15;264(35):21087–21090. [PubMed] [Google Scholar]
  2. Caldwell H. D., Kromhout J., Schachter J. Purification and partial characterization of the major outer membrane protein of Chlamydia trachomatis. Infect Immun. 1981 Mar;31(3):1161–1176. doi: 10.1128/iai.31.3.1161-1176.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ceballos M. M., Hatch T. P. Use of HeLa cell guanine nucleotides by Chlamydia psittaci. Infect Immun. 1979 Jul;25(1):98–102. doi: 10.1128/iai.25.1.98-102.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fan H. Z., McClarty G., Brunham R. C. Biochemical evidence for the existence of thymidylate synthase in the obligate intracellular parasite Chlamydia trachomatis. J Bacteriol. 1991 Nov;173(21):6670–6677. doi: 10.1128/jb.173.21.6670-6677.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fan H., Brunham R. C., McClarty G. Acquisition and synthesis of folates by obligate intracellular bacteria of the genus Chlamydia. J Clin Invest. 1992 Nov;90(5):1803–1811. doi: 10.1172/JCI116055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fraiz J., Jones R. B. Chlamydial infections. Annu Rev Med. 1988;39:357–370. doi: 10.1146/annurev.me.39.020188.002041. [DOI] [PubMed] [Google Scholar]
  7. Green C. D., Martin D. W., Jr Characterization of a feedback-resistant phosphoribosylpyrophosphate synthetase from cultured, mutagenized hepatoma cells that overproduce purines. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3698–3702. doi: 10.1073/pnas.70.12.3698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hassan H. F., Coombs G. H. Purine and pyrimidine metabolism in parasitic protozoa. FEMS Microbiol Rev. 1988 Feb;4(1):47–83. doi: 10.1111/j.1574-6968.1988.tb02708.x-i1. [DOI] [PubMed] [Google Scholar]
  9. Hatch T. P., Al-Hossainy E., Silverman J. A. Adenine nucleotide and lysine transport in Chlamydia psittaci. J Bacteriol. 1982 May;150(2):662–670. doi: 10.1128/jb.150.2.662-670.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hatch T. P. Utilization of L-cell nucleoside triphosphates by Chlamydia psittaci for ribonucleic acid synthesis. J Bacteriol. 1975 May;122(2):393–400. doi: 10.1128/jb.122.2.393-400.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hatch T. P. Utilization of exogenous thymidine by Chlamydia psittaci growing in the thymidine kinase-containing and thymidine kinase-deficient L cells. J Bacteriol. 1976 Feb;125(2):706–712. doi: 10.1128/jb.125.2.706-712.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Houghton P. J., Germain G. S., Hazelton B. J., Pennington J. W., Houghton J. A. Mutants of human colon adenocarcinoma, selected for thymidylate synthase deficiency. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1377–1381. doi: 10.1073/pnas.86.4.1377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Khym J. X. An analytical system for rapid separation of tissue nucleotides at low pressures on conventional anion exchangers. Clin Chem. 1975 Aug;21(9):1245–1252. [PubMed] [Google Scholar]
  14. Krungkrai J., Yuthavong Y., Webster H. K. High-performance liquid chromatographic assay for thymidylate synthase from the human malaria parasite, Plasmodium falciparum. J Chromatogr. 1989 Jan 27;487(1):51–59. doi: 10.1016/s0378-4347(00)83006-6. [DOI] [PubMed] [Google Scholar]
  15. McClarty G., Fan H., Andersen A. A. Diversity in nucleotide acquisition by antigenically similar Chlamydia psittaci of avian origin. FEMS Microbiol Lett. 1993 Apr 15;108(3):325–331. doi: 10.1111/j.1574-6968.1993.tb06123.x. [DOI] [PubMed] [Google Scholar]
  16. McClarty G., Tipples G. In situ studies on incorporation of nucleic acid precursors into Chlamydia trachomatis DNA. J Bacteriol. 1991 Aug;173(16):4922–4931. doi: 10.1128/jb.173.16.4922-4931.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mitchell A., Finch L. R. Pathways of nucleotide biosynthesis in Mycoplasma mycoides subsp. mycoides. J Bacteriol. 1977 Jun;130(3):1047–1054. doi: 10.1128/jb.130.3.1047-1054.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Moulder J. W. Interaction of chlamydiae and host cells in vitro. Microbiol Rev. 1991 Mar;55(1):143–190. doi: 10.1128/mr.55.1.143-190.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nelson D. J., LaFon S. W., Tuttle J. V., Miller W. H., Miller R. L., Krenitsky T. A., Elion G. B., Berens R. L., Marr J. J. Allopurinol ribonucleoside as an antileishmanial agent. Biological effects, metabolism, and enzymatic phosphorylation. J Biol Chem. 1979 Nov 25;254(22):11544–11549. [PubMed] [Google Scholar]
  20. Patterson D., Carnright D. V. Biochemical genetic analysis of pyrimidine biosynthesis in mammalian cells: I. Isolation of a mutant defective in the early steps of de novo pyrimidine synthesis. Somatic Cell Genet. 1977 Sep;3(5):483–495. doi: 10.1007/BF01539120. [DOI] [PubMed] [Google Scholar]
  21. Qin B., McClarty G. Effect of 6-thioguanine on Chlamydia trachomatis growth in wild-type and hypoxanthine-guanine phosphoribosyltransferase-deficient cells. J Bacteriol. 1992 May;174(9):2865–2873. doi: 10.1128/jb.174.9.2865-2873.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Reyes P., Rathod P. K., Sanchez D. J., Mrema J. E., Rieckmann K. H., Heidrich H. G. Enzymes of purine and pyrimidine metabolism from the human malaria parasite, Plasmodium falciparum. Mol Biochem Parasitol. 1982 May;5(5):275–290. doi: 10.1016/0166-6851(82)90035-4. [DOI] [PubMed] [Google Scholar]
  23. Schachter J. The intracellular life of Chlamydia. Curr Top Microbiol Immunol. 1988;138:109–139. [PubMed] [Google Scholar]
  24. Schwartzman J. D., Pfefferkorn E. R. Pyrimidine synthesis by intracellular Toxoplasma gondii. J Parasitol. 1981 Apr;67(2):150–158. [PubMed] [Google Scholar]
  25. Tipples G., McClarty G. Isolation and initial characterization of a series of Chlamydia trachomatis isolates selected for hydroxyurea resistance by a stepwise procedure. J Bacteriol. 1991 Aug;173(16):4932–4940. doi: 10.1128/jb.173.16.4932-4940.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tribby I. I., Moulder J. W. Availability of bases and nucleosides as precursors of nucleic acids in L cells and in the agent of meningopneumonitis. J Bacteriol. 1966 Jun;91(6):2362–2367. doi: 10.1128/jb.91.6.2362-2367.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Urlaub G., Chasin L. A. Isolation of Chinese hamster cell mutants deficient in dihydrofolate reductase activity. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4216–4220. doi: 10.1073/pnas.77.7.4216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wang C. C. Parasite enzymes as potential targets for antiparasitic chemotherapy. J Med Chem. 1984 Jan;27(1):1–9. doi: 10.1021/jm00367a001. [DOI] [PubMed] [Google Scholar]
  29. Wang C. C., Simashkevich P. M. Purine metabolism in the protozoan parasite Eimeria tenella. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6618–6622. doi: 10.1073/pnas.78.11.6618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wang C. C., Verham R., Tzeng S. F., Aldritt S., Cheng H. W. Pyrimidine metabolism in Tritrichomonas foetus. Proc Natl Acad Sci U S A. 1983 May;80(9):2564–2568. doi: 10.1073/pnas.80.9.2564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Weiss E. The biology of rickettsiae. Annu Rev Microbiol. 1982;36:345–370. doi: 10.1146/annurev.mi.36.100182.002021. [DOI] [PubMed] [Google Scholar]
  32. Winkler H. H. Rickettsia species (as organisms). Annu Rev Microbiol. 1990;44:131–153. doi: 10.1146/annurev.mi.44.100190.001023. [DOI] [PubMed] [Google Scholar]

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