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Characterization of a Mutant of Toxoplasma gondii Resistant to Aphidicolin 1
Author(s) -
PFEFFERKORN E. R.
Publication year - 1984
Publication title -
the journal of protozoology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.067
H-Index - 77
eISSN - 1550-7408
pISSN - 0022-3921
DOI - 10.1111/j.1550-7408.1984.tb02967.x
Subject(s) - aphidicolin , toxoplasma gondii , mutant , biology , dna synthesis , microbiology and biotechnology , dna , wild type , biochemistry , genetics , antibody , gene
Aphidicolin, a mycotoxin that inhibits eucaryotic DNA polymerase alpha, blocked the growth of Toxoplasma gondii in confluent cultured human fibroblasts. Aphidicolin immediately inhibited DNA synthesis by T. gondii while it had a delayed and less dramatic effect on RNA synthesis. A mutant of T. gondii resistant to aphidicolin was isolated with the aid of mutagenesis by ethylnitrosourea. Parasite growth measured three days after drug treatment and parasite DNA synthesis measured immediately after drug treatment were, respectively, five‐ and four‐fold more resistant to aphidicolin in the mutant as compared with the wild type parasite. The mutant had a three‐fold greater capacity than the wild type to incorporate uracil into its deoxycytidine triphosphate pool. This increased deoxycytidine triphosphate pool is the probable explanation for the mutant's resistance because this deoxynucleotide is known, in mammalian cells, to reverse the inhibition of DNA synthesis by aphidicolin in a competitive manner.