Toxoplasma gondii: genetic recombination between drug resistant mutants |
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Authors: | L C Pfefferkorn E R Pfefferkorn |
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Institution: | Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA |
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Abstract: | Mutants resistant to adenine arabinoside (ara-A) or to 5-fluorodeoxyuridine (FUDR) were isolated from a newly isolated oocyst producing strain of Toxoplasma gondii. The selection and characterization of these mutants were carried out in human fibroblast cultures. The ara-A-resistant mutant lacked the enzyme adenosine kinase. The biochemical basis of FUDR resistance remains unknown. Both mutants were used to infect mice to produce brain cysts that contained bradyzoites. Mouse brains that contained cysts were fed to kittens to complete the sexual cycle of T. gondii. Those kittens fed cysts of only one drug-resistant mutant excreted oocysts that yielded no detectable recombinant doubly resistant parasites that could make plaques in the presence of both ara-A and FUDR. Kittens fed a mixture of cysts that contained both mutants excreted oocysts that contained approximately 12% doubly resistant parasites. The reciprocal recombinant, sensitive to both drugs, was also isolated. The doubly resistant recombinant was totally deficient in adenosine kinase activity. This pattern of inheritance is consistant only with a haploid genome for all stages of T. gondii except the zygote formed by fusion of gametes and the unsporulated oocyst. Two FUDR-resistant mutants were also defective in the production of oocysts. These mutants failed to recombine with an ara-A-resistant mutant of proven fertility and thus their inability to make oocysts must result from a defect in the production of both microgametes and macrogametes. |
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Keywords: | Protozoa parasitic wild type mutant resistant to adenine arabinoside mutant resistant to 5-fluorodeoxyuridine Fibroblast human Cell culture Genetic recombination Adenine arabinoside 5-Fluorodeoxyuridine Adenosine kinase (EC 2 7 1 20) Uracil phosphoribosyltransferase (EC 2 4 2 9) |
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