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Conditional antifolate resistance in Bacillus subtilis thyA.

J L Farmer

    Antimicrobial Agents and Chemotherapy
    |April 1, 1979
    PubMed
    Summary
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    Antifolate resistance in Bacillus subtilis is linked to the afo mutation. Conditional resistance in thyA afo strains may stem from thymidylate synthetase B

    Area of Science:

    • Microbiology
    • Molecular Biology
    • Biochemistry

    Background:

    • Antifolates are drugs that target folate metabolism.
    • Bacillus subtilis can develop resistance to antifolates through specific mutations.
    • The antifolate resistance (afo) mutation is a key factor in B. subtilis antifolate resistance.

    Purpose of the Study:

    • To investigate the mechanisms of antifolate resistance in Bacillus subtilis.
    • To elucidate the role of the afo mutation and thymidylate synthetase B in conditional resistance.
    • To analyze folate metabolism and dihydrofolate reductase in resistant strains.

    Main Methods:

    • Genetic analysis of Bacillus subtilis strains.
    • Folatemetabolism studies in methotrexate-treated cells.

    Related Experiment Videos

  • Enzyme kinetic analysis of thymidylate synthetase B.
  • Characterization of dihydrofolate reductase from resistant mutants.

    • Main Results:

    • The afo mutation confers unconditional antifolate resistance in B. subtilis.
    • Conditional resistance in thyA afo strains is hypothesized to involve thymidylate synthetase B with high substrate K(m).
    • Most thymine-requiring B. subtilis mutants were identified as afo; dihydrofolate reductase analysis did not reveal resistance mechanisms.

    Conclusions:

    • The afo mutation is central to antifolate resistance in B. subtilis.
    • Thymidylate synthetase B's kinetic properties are implicated in conditional antifolate resistance.
    • Further research is needed to fully understand antifolate resistance mechanisms in B. subtilis.