Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 May 10;91(10):4244–4248. doi: 10.1073/pnas.91.10.4244

Auxotrophs of Plasmodium falciparum dependent on p-aminobenzoic acid for growth.

G A McConkey 1, I Ittarat 1, S R Meshnick 1, T F McCutchan 1
PMCID: PMC43761  PMID: 8183896

Abstract

The isolation of auxotrophic strains of a parasite offers new opportunities for studying parasitology. We have isolated cloned lines of Plasmodium falciparum that, unlike the parent line from which they were derived, rely on exogenous p-aminobenzoic acid (PABA) for growth. Isolation involved random mutagenesis of a cloned line of P. falciparum and subsequent selection of PABA-dependent parasites. Both parent and PABA-dependent clones were analyzed for PABA uptake and synthesis. Each clone takes up comparable amounts of PABA from the medium. The parent line, clone 3D7, can synthesize PABA de novo, whereas the PABA-dependent clones cannot. The requirement of exogenous PABA for growth by the auxotrophic strains coupled with their inability to synthesize PABA indicates that normal parasite growth can be completely supported by either synthesis or salvage. This work further clarifies the relationship between the availability of PABA and success of the parasite, an issue of debate from classic studies showing reduced parasite load in individuals on milk-fed diets.

Full text

PDF
4244

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  2. Chatfield S., Roberts M., Londono P., Cropley I., Douce G., Dougan G. The development of oral vaccines based on live attenuated Salmonella strains. FEMS Immunol Med Microbiol. 1993 Jun;7(1):1–7. doi: 10.1111/j.1574-695X.1993.tb00374.x. [DOI] [PubMed] [Google Scholar]
  3. Cárdenas L., Clements J. D. Stability, immunogenicity and expression of foreign antigens in bacterial vaccine vectors. Vaccine. 1993;11(2):126–135. doi: 10.1016/0264-410x(93)90007-k. [DOI] [PubMed] [Google Scholar]
  4. Dieckmann A., Jung A. Mechanisms of sulfadoxine resistance in Plasmodium falciparum. Mol Biochem Parasitol. 1986 May;19(2):143–147. doi: 10.1016/0166-6851(86)90119-2. [DOI] [PubMed] [Google Scholar]
  5. HAWKING F. Milk, p-aminobenzoate, and malaria of rats and monkeys. Br Med J. 1954 Feb 20;1(4859):425–429. doi: 10.1136/bmj.1.4859.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hoiseth S. K., Stocker B. A. Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines. Nature. 1981 May 21;291(5812):238–239. doi: 10.1038/291238a0. [DOI] [PubMed] [Google Scholar]
  7. Inselburg J. Isolation of temperature-sensitive mutants of Plasmodium falciparum. Mol Biochem Parasitol. 1985 Jun;16(1):75–83. doi: 10.1016/0166-6851(85)90050-7. [DOI] [PubMed] [Google Scholar]
  8. Inselburg J., Rossan R. N., Escajadillo A. Growth and immunity conferred by a Plasmodium falciparum temperature sensitive mutant in Panamanian owl monkeys. Am J Trop Med Hyg. 1989 May;40(5):465–469. doi: 10.4269/ajtmh.1989.40.465. [DOI] [PubMed] [Google Scholar]
  9. JACOBS R. L. ROLE OF P-AMINOBENZOIC ACID IN PLASMODIUM BERGHEI INFECTION IN THE MOUSE. Exp Parasitol. 1964 Jun;15:213–225. doi: 10.1016/0014-4894(64)90017-7. [DOI] [PubMed] [Google Scholar]
  10. Kretschmar W., Voller A. Suppression of Plasmodium falciparum malaria in Aotus monkeys by milk diet. Z Tropenmed Parasitol. 1973 Mar;24(1):51–59. [PubMed] [Google Scholar]
  11. Lambros C., Vanderberg J. P. Synchronization of Plasmodium falciparum erythrocytic stages in culture. J Parasitol. 1979 Jun;65(3):418–420. [PubMed] [Google Scholar]
  12. Lindsay R. M., McLaren A. M., Baty J. D. Reversed-phase high-performance liquid chromatographic assay for the determination of the in vitro acetylation of p-aminobenzoic acid by human whole blood. J Chromatogr. 1988 Dec 9;433:292–297. doi: 10.1016/s0378-4347(00)80611-8. [DOI] [PubMed] [Google Scholar]
  13. McCutchan T. F. Pyrimethamine resistance in malaria parasites. Parasitol Today. 1988 Mar;4(3):64–65. doi: 10.1016/0169-4758(88)90195-0. [DOI] [PubMed] [Google Scholar]
  14. Milhous W. K., Weatherly N. F., Bowdre J. H., Desjardins R. E. In vitro activities of and mechanisms of resistance to antifol antimalarial drugs. Antimicrob Agents Chemother. 1985 Apr;27(4):525–530. doi: 10.1128/aac.27.4.525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nowell F. The effect of a milk diet upon Plasmodium berghei, Nuttallia (=Babesia) rodhaini and Trypanosoma brucei infections in mice. Parasitology. 1970 Dec;61(3):425–433. doi: 10.1017/s0031182000041275. [DOI] [PubMed] [Google Scholar]
  16. Stocker B. A. Auxotrophic Salmonella typhi as live vaccine. Vaccine. 1988 Apr;6(2):141–145. doi: 10.1016/s0264-410x(88)80017-3. [DOI] [PubMed] [Google Scholar]
  17. Trager W., Jensen J. B. Human malaria parasites in continuous culture. Science. 1976 Aug 20;193(4254):673–675. doi: 10.1126/science.781840. [DOI] [PubMed] [Google Scholar]
  18. Zhang Y., Merali S., Meshnick S. R. p-Aminobenzoic acid transport by normal and Plasmodium falciparum-infected erythrocytes. Mol Biochem Parasitol. 1992 Jun;52(2):185–194. doi: 10.1016/0166-6851(92)90051-k. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES