Abstract
Resistance to antifolates in Bacillus subtilis strains results from the presence of an antifolate resistance mutation (afo). Strains which are thyA+afo are unconditionally resistant to antifolates. The conditional resistance of thyA afo strains is hypothesized to be due to the thyB+ gene product (thymidylate synthetase B) having a high Km 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 of afo+ cells to methotrexate suggested that most, if not all, B. subtilis thymine-requiring mutants are afo. Analysis of dihydrofolate reductase from afo cells did not reveal an obvious mechanism for antifolate resistance in those cells.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anagnostopoulos C., Schneider-Champagne A. M. Déterminisme génétique de l'exigence en thymine chez certains mutants de Bacillus subtilis. C R Acad Sci Hebd Seances Acad Sci D. 1966 Mar 14;262(11):1311–1314. [PubMed] [Google Scholar]
- Anagnostopoulos C., Spizizen J. REQUIREMENTS FOR TRANSFORMATION IN BACILLUS SUBTILIS. J Bacteriol. 1961 May;81(5):741–746. doi: 10.1128/jb.81.5.741-746.1961. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buehring K. U., Tamura T., Stokstad E. L. Folate coenzymes of Lactobacillus casei and Streptococcus faecalis. J Biol Chem. 1974 Feb 25;249(4):1081–1089. [PubMed] [Google Scholar]
- FARMER J. L., ROTHMAN F. TRANSFORMABLE THYMINE-REQUIRING MUTANT OF BACILLUS SUBTILS. J Bacteriol. 1965 Jan;89:262–263. doi: 10.1128/jb.89.1.262-263.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Herbert V. Aseptic addition method for Lactobacillus casei assay of folate activity in human serum. J Clin Pathol. 1966 Jan;19(1):12–16. doi: 10.1136/jcp.19.1.12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hintze D. N., Farmer J. L. Identification of poly-gamma-glutamyl chain lengths in folates of Bacillus subtilis. J Bacteriol. 1975 Dec;124(3):1236–1239. doi: 10.1128/jb.124.3.1236-1239.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neuhard J., Price A. R., Schack L., Thomassen E. Two thymidylate synthetases in Bacillus subtilis. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1194–1198. doi: 10.1073/pnas.75.3.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shin Y. S., Buehring K. U., Stokstad E. L. The metabolism of methotrexate in Lactobacillus casei and rat liver and the influence of methotrexate on metabolism of folic acid. J Biol Chem. 1974 Sep 25;249(18):5772–5777. [PubMed] [Google Scholar]
- Wilson M. C., Farmer J. L., Rothman F. Thymidylate synthesis and aminopterin resistance in Bacillus subtilis. J Bacteriol. 1966 Jul;92(1):186–196. doi: 10.1128/jb.92.1.186-196.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
