Open AccessConditional Antifolate Resistance in Bacillus subtilis thyA
Author(s) -
James L. Farmer
Publication year - 1979
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.15.4.527
Subject(s) - antifolate , dihydrofolate reductase , bacillus subtilis , thymidylate synthase , biology , genetics , mutant , methotrexate , antimetabolite , microbiology and biotechnology , gene , bacteria , chemotherapy , immunology , fluorouracil
Resistance to antifolates inBacillus subtilis strains results from the presence of an antifolate resistance mutation (afo ). Strains which arethyA + afo are unconditionally resistant to antifolates. The conditional resistance ofthyA afo strains is hypothesized to be due to thethyB + gene product (thymidylate synthetase B) having a highKm for the folate substrate, thus leading to thymineless death in the presence of antifolates. An alternative model for conditional antifolate resistance was shown to be incorrect by analysis of folate metabolism in methotrexate-treated cells. Genetic analysis and studies of the response ofafo + cells to methotrexate suggested that most, if not all,B. subtilis thymine-requiring mutants areafo . Analysis of dihydrofolate reductase fromafo cells did not reveal an obvious mechanism for antifolate resistance in those cells.