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Trimethoprim resistance transposon Tn 4003 from Staphylococcus aureus encodes genes for a dihydrofolate reductase and thymidylate synthetase flanked by three copies of IS 257
Abstract
Summary: Trimethoprim resistance mediated by the Staphylococcus aureus multi‐resistance plasmid pSK1 is encoded by a structure with characteristics of a composite transposon which we have designated Tn 4003. Nucleotide sequence analysis of Tn 4003 revealed it to be 4717 bp in length and to contain three copies of the insertion element IS 257 (789‐790 bp), the outside two of which are flanked by directly repeated 8‐bp target sequences. IS 257 has imperfect terminal inverted repeats of 27‐28 bp and encodes for a putative transposase with two potential α‐helix‐turn‐α‐helix DNA recognition motifs. IS 257 shares sequence similarities with members of the IS 15 family of insertion sequences from Gram‐negative bacteria and with ISS 1 from Streptococcus lactis. The central region of the transposon contains the dfrA gene that specifies the S1 dihydrofolate reductase (DHFR) responsible for trimethoprim resistance. The S1 enzyme shows sequence homology with type I and V trimethoprim‐resistant DHFRs from Gram‐negative bacteria and with chromosomally encoded DHFRs from Gram‐positive and Gram‐negative bacteria. 5’to dfrA is a thymidylate synthetase gene, designated thyE.
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“The cause of trimethoprim resistance is the synthesis of dihydrofolate reductase (DHFRS1) (EC 1.5.1.3) encoded in S. aureus by dfrA, dfrK, the cassette genes dfrA12 and dfr15 [8,9,119,120,199] and dfrG found in SCCmec [63].”
From Molecular Mechanisms of Drug Resistance in Staphylococcus aureus (2022) · cites this paper as [199]
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Metadata
- Authors
- Rouch, D. A., Messerotti, L. J., Loo, L. S. L., Jackson, C. A., & Skurray, R. A.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 1989-02
- Volume
- 3
- Issue
- 2
- Pages
- 161-175
- ISSN
- 0950-382X
- 1365-2958
- Cited by
- 131
- References
- 0
- Language
- en
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- Rouch, D. A., Messerotti, L. J., Loo, L. S. L., Jackson, C. A., & Skurray, R. A. (1989). Trimethoprim resistance transposon Tn 4003 from Staphylococcus aureus encodes genes for a dihydrofolate reductase and thymidylate synthetase flanked by three copies of IS 257. Molecular Microbiology. https://doi.org/10.1111/j.1365-2958.1989.tb01805.x
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