Characterization of trimethoprim- and sulphisoxazole-resistant Chlamydia trachomatis.
Trimethoprim and sulphisoxazole were used as selective agents in culture to isolate, by a stepwise procedure, a series of Chlamydia trachomatis L2 populations resistant to the cytotoxic effects of the drugs. Two trimethoprim-resistant populations, L2TriR-60 and L2TriR-100, and one sulphonamide-resistant population, L2SulfR-100, were characterized in more detail. In addition to being resistant to trimethoprim, L2TriR-60 was cross-resistant to methotrexate, sensitive to sulphisoxazole and displayed a ribonucleotide auxotrophy similar to that of its parental wild type, C. trachomatis L2. Surprisingly, L2TriR-100 and L2SulfR-100 appeared phenotypically identical. Both mutants were highly resistant to trimethoprim, sulphisoxazole, and methotrexate. In contrast to wild-type C. trachomatis L2, these populations were sensitive to 5-fluorouracil. L2TriR-100 and L2SulfR-100 were incapable of taking pyrimidine ribonucleotides from the host cell and no longer synthesized thymidine nucleotides de novo. The pyrimidine requirement of these mutants was met by salvaging host-cell uracil and thymidine, a property which can account for their drug-resistant characteristics. L2TriR-100 and L2SulfR-100 could also salvage adenine and guanine. Using L2TriR-100 as a starting stock, a mutant population resistant to the cytotoxic effects of trimethoprim and 5-fluorouracil (L2Tri/5-FU) was selected. L2Tri/5-FU was resistant to 5-fluorouracil because it had regained the capacity to take pyrimidine ribonucleotides from the host cell.
Wang
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LL
Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
Henson
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E
McClarty
G
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002692:Chlamydia trachomatis / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D004269:DNA, Bacterial / Q000096:biosynthesis; D004352:Drug Resistance, Microbial; D005472:Fluorouracil / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism; D007739:L Cells; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010641:Phenotype; D012329:RNA, Bacterial / Q000096:biosynthesis; D013444:Sulfisoxazole / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014295:Trimethoprim / Q000494:pharmacology*; D014498:Uracil / Q000378:metabolism; D015215:Zidovudine / Q000494:pharmacology
D004269:DNA, Bacterial; D012329:RNA, Bacterial; D015215:Zidovudine; D014498:Uracil; D013444:Sulfisoxazole; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D014295:Trimethoprim; D005472:Fluorouracil; D013936:Thymidine; D008727:Methotrexate