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. 1995 Jan;39(1):112–116. doi: 10.1128/aac.39.1.112

Sequence identity with type VIII and association with IS176 of type IIIc dihydrofolate reductase from Shigella sonnei.

N L Barg 1, S Register 1, C Thomson 1, S Amyes 1
PMCID: PMC162495  PMID: 7695291

Abstract

An uncommon dihydrofolate reductase (DHFR), type IIIc, was coded for by Shigella sonnei that harbors plasmid pBH700 and that was isolated in North Carolina. The trimethoprim resistance gene carried on pBH700 was subcloned and sequenced. The nucleotide sequence of the gene encoding type IIIc DHFR was identical to the gene encoding type VIII DHFR. The type IIIc amino acid sequence was approximately 50% similar to those of DHFRs commonly found in enteric bacteria. Furthermore, this gene was flanked by IS176 (IS26), an insertion sequence usually associated with those of aminoglycoside resistance genes. The gene for type IIIc DHFR was located by hybridization within a 1,993-bp PstI fragment in each of eight conjugative plasmids from geographically diverse strains of S. sonnei. Each plasmid also conferred resistance to ampicillin, streptomycin, and sulfamethoxazole and belonged to incompatibility group M. Plasmids carrying this new trimethoprim resistance gene, which is uniquely associated with IS176, have disseminated throughout the United States.

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Selected References

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  1. Amyes S. G., Smith J. T. R-factor mediated dihydrofolate reductases which confer trimethoprim resistance. J Gen Microbiol. 1978 Aug;107(2):263–271. doi: 10.1099/00221287-107-2-263. [DOI] [PubMed] [Google Scholar]
  2. Amyes S. G., Smith J. T. R-factor trimethoprim resistance mechanism: an insusceptible target site. Biochem Biophys Res Commun. 1974 May 20;58(2):412–418. doi: 10.1016/0006-291x(74)90380-5. [DOI] [PubMed] [Google Scholar]
  3. Amyes S. G., Smith J. T. The purification and properties of the trimethoprim-resistant dihydrofolate reductase mediated by the R-factor, R388. Eur J Biochem. 1976 Jan 15;61(2):597–603. doi: 10.1111/j.1432-1033.1976.tb10055.x. [DOI] [PubMed] [Google Scholar]
  4. Amyes S. G., Towner K. J., Young H. K. Classification of plasmid-encoded dihydrofolate reductases conferring trimethoprim resistance. J Med Microbiol. 1992 Jan;36(1):1–3. doi: 10.1099/00222615-36-1-1. [DOI] [PubMed] [Google Scholar]
  5. Barg N. L., Hutson F. S., Wheeler L. A., Thomson C. J., Amyes S. G., Wharton M., Schaffner W. Novel dihydrofolate reductases isolated from epidemic strains of trimethoprim/sulfamethoxazole-resistant Shigella sonnei. J Infect Dis. 1990 Aug;162(2):466–473. doi: 10.1093/infdis/162.2.466. [DOI] [PubMed] [Google Scholar]
  6. Bratoeva M. P., John J. F., Jr Dissemination of trimethoprim-resistant clones of Shigella sonnei in Bulgaria. J Infect Dis. 1989 Apr;159(4):648–653. doi: 10.1093/infdis/159.4.648. [DOI] [PubMed] [Google Scholar]
  7. Burdeska A., Ott M., Bannwarth W., Then R. L. Identical genes for trimethoprim-resistant dihydrofolate reductase from Staphylococcus aureus in Australia and central Europe. FEBS Lett. 1990 Jun 18;266(1-2):159–162. doi: 10.1016/0014-5793(90)81529-w. [DOI] [PubMed] [Google Scholar]
  8. Chatkaeomorakot A., Echeverria P., Taylor D. N., Seriwatana J., Leksomboon U. Trimethoprim-resistant Shigella and enterotoxigenic Escherichia coli strains in children in Thailand. Pediatr Infect Dis J. 1987 Aug;6(8):735–739. doi: 10.1097/00006454-198708000-00008. [DOI] [PubMed] [Google Scholar]
  9. Datta N., Barth P. T. Compatibility properties of R483, a member of the I plasmid complex. J Bacteriol. 1976 Mar;125(3):796–799. doi: 10.1128/jb.125.3.796-799.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Delgado R., Otero J. R. High-level resistance to trimethoprim in Shigella sonnei associated with plasmid-encoded dihydrofolate reductase type I. Antimicrob Agents Chemother. 1988 Oct;32(10):1598–1599. doi: 10.1128/aac.32.10.1598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fling M. E., Kope J., Richards C. Characterization of plasmid pAZ1 and the type III dihydrofolate reductase gene. Plasmid. 1988 Jan;19(1):30–38. doi: 10.1016/0147-619x(88)90060-1. [DOI] [PubMed] [Google Scholar]
  12. Fling M. E., Richards C. The nucleotide sequence of the trimethoprim-resistant dihydrofolate reductase gene harbored by Tn7. Nucleic Acids Res. 1983 Aug 11;11(15):5147–5158. doi: 10.1093/nar/11.15.5147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Goldstein F. W., Papadopoulou B., Acar J. F. The changing pattern of trimethoprim resistance in Paris, with a review of worldwide experience. Rev Infect Dis. 1986 Sep-Oct;8(5):725–737. doi: 10.1093/clinids/8.5.725. [DOI] [PubMed] [Google Scholar]
  14. Griffin P. M., Tauxe R. V., Redd S. C., Puhr N. D., Hargrett-Bean N., Blake P. A. Emergence of highly trimethoprim-sulfamethoxazole-resistant Shigella in a native American population: an epidemiologic study. Am J Epidemiol. 1989 May;129(5):1042–1051. doi: 10.1093/oxfordjournals.aje.a115208. [DOI] [PubMed] [Google Scholar]
  15. Hanahan D. Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983 Jun 5;166(4):557–580. doi: 10.1016/s0022-2836(83)80284-8. [DOI] [PubMed] [Google Scholar]
  16. Hansen J. B., Olsen R. H. Isolation of large bacterial plasmids and characterization of the P2 incompatibility group plasmids pMG1 and pMG5. J Bacteriol. 1978 Jul;135(1):227–238. doi: 10.1128/jb.135.1.227-238.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Heikkilä E., Skurnik M., Sundström L., Huovinen P. A novel dihydrofolate reductase cassette inserted in an integron borne on a Tn21-like element. Antimicrob Agents Chemother. 1993 Jun;37(6):1297–1304. doi: 10.1128/aac.37.6.1297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Heikkilä E., Sundström L., Skurnik M., Huovinen P. Analysis of genetic localization of the type I trimethoprim resistance gene from Escherichia coli isolated in Finland. Antimicrob Agents Chemother. 1991 Aug;35(8):1562–1569. doi: 10.1128/aac.35.8.1562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Iida S., Meyer J., Linder P., Goto N., Nakaya R., Reif H. J., Arber W. The kanamycin resistance transposon Tn2680 derived from the R plasmid Rts1 and carried by phage P1Km has flanking 0.8-kb-long direct repeats. Plasmid. 1982 Sep;8(2):187–198. doi: 10.1016/0147-619x(82)90056-7. [DOI] [PubMed] [Google Scholar]
  20. Jansson C., Franklin A., Sköld O. Spread of a newly found trimethoprim resistance gene, dhfrIX, among porcine isolates and human pathogens. Antimicrob Agents Chemother. 1992 Dec;36(12):2704–2708. doi: 10.1128/aac.36.12.2704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lévesque C., Piché L., Larose C., Roy P. H. PCR mapping of integrons reveals several novel combinations of resistance genes. Antimicrob Agents Chemother. 1995 Jan;39(1):185–191. doi: 10.1128/aac.39.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Messing J., Crea R., Seeburg P. H. A system for shotgun DNA sequencing. Nucleic Acids Res. 1981 Jan 24;9(2):309–321. doi: 10.1093/nar/9.2.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Murray B. E. Resistance of Shigella, Salmonella, and other selected enteric pathogens to antimicrobial agents. Rev Infect Dis. 1986 May-Jun;8 (Suppl 2):S172–S181. doi: 10.1093/clinids/8.supplement_2.s172. [DOI] [PubMed] [Google Scholar]
  24. Parsons Y., Hall R. M., Stokes H. W. A new trimethoprim resistance gene, dhfrX, in the In7 integron of plasmid pDGO100. Antimicrob Agents Chemother. 1991 Nov;35(11):2436–2439. doi: 10.1128/aac.35.11.2436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rouch D. A., Messerotti L. J., Loo L. S., Jackson C. A., Skurray R. A. Trimethoprim resistance transposon Tn4003 from Staphylococcus aureus encodes genes for a dihydrofolate reductase and thymidylate synthetase flanked by three copies of IS257. Mol Microbiol. 1989 Feb;3(2):161–175. doi: 10.1111/j.1365-2958.1989.tb01805.x. [DOI] [PubMed] [Google Scholar]
  26. Rouch D. A., Skurray R. A. IS257 from Staphylococcus aureus: member of an insertion sequence superfamily prevalent among gram-positive and gram-negative bacteria. Gene. 1989;76(2):195–205. doi: 10.1016/0378-1119(89)90160-1. [DOI] [PubMed] [Google Scholar]
  27. Singh K. V., Reves R. R., Pickering L. K., Murray B. E. Identification by DNA sequence analysis of a new plasmid-encoded trimethoprim resistance gene in fecal Escherichia coli isolates from children in day-care centers. Antimicrob Agents Chemother. 1992 Aug;36(8):1720–1726. doi: 10.1128/aac.36.8.1720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sundström L., Rådström P., Swedberg G., Sköld O. Site-specific recombination promotes linkage between trimethoprim- and sulfonamide resistance genes. Sequence characterization of dhfrV and sulI and a recombination active locus of Tn21. Mol Gen Genet. 1988 Aug;213(2-3):191–201. doi: 10.1007/BF00339581. [DOI] [PubMed] [Google Scholar]
  29. Sundström L., Sköld O. The dhfrI trimethoprim resistance gene of Tn7 can be found at specific sites in other genetic surroundings. Antimicrob Agents Chemother. 1990 Apr;34(4):642–650. doi: 10.1128/aac.34.4.642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sundström L., Swedberg G., Sköld O. Characterization of transposon Tn5086, carrying the site-specifically inserted gene dhfrVII mediating trimethoprim resistance. J Bacteriol. 1993 Mar;175(6):1796–1805. doi: 10.1128/jb.175.6.1796-1805.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sundström L., Vinayagamoorthy T., Sköld O. Novel type of plasmid-borne resistance to trimethoprim. Antimicrob Agents Chemother. 1987 Jan;31(1):60–66. doi: 10.1128/aac.31.1.60. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Takahashi S., Nagano Y. Rapid procedure for isolation of plasmid DNA and application to epidemiological analysis. J Clin Microbiol. 1984 Oct;20(4):608–613. doi: 10.1128/jcm.20.4.608-613.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Thomson C. J., Barg N., Amyes S. G. N-terminal amino acid sequence of the novel type IIIb trimethoprim-resistant plasmid-encoded dihydrofolate reductase from Shigella sonnei. J Gen Microbiol. 1990 Apr;136(4):673–677. doi: 10.1099/00221287-136-4-673. [DOI] [PubMed] [Google Scholar]
  34. Thomson C. J. Trimethoprim and brodimoprim resistance of gram-positive and gram-negative bacteria. J Chemother. 1993 Dec;5(6):458–464. [PubMed] [Google Scholar]
  35. Thomson C. J., Young H. K., Amyes S. G. N-terminal amino-acid sequence and subunit structure of the type IV trimethoprim-resistant plasmid-encoded dihydrofolate reductase. J Med Microbiol. 1990 Jul;32(3):153–158. doi: 10.1099/00222615-32-3-153. [DOI] [PubMed] [Google Scholar]
  36. Tsakris A., Johnson A. P., Legakis N. J., Tzouvelekis L. S. Prevalence of the type I and type II DHFR genes in trimethoprim-resistant urinary isolates of Escherichia coli from Greece. J Antimicrob Chemother. 1993 May;31(5):665–671. doi: 10.1093/jac/31.5.665. [DOI] [PubMed] [Google Scholar]
  37. Wrighton C. J., Strike P. A pathway for the evolution of the plasmid NTP16 involving the novel kanamycin resistance transposon Tn4352. Plasmid. 1987 Jan;17(1):37–45. doi: 10.1016/0147-619x(87)90006-0. [DOI] [PubMed] [Google Scholar]
  38. Wylie B. A., Koornhof H. J. Nucleotide sequence of dihydrofolate reductase type VI. J Med Microbiol. 1991 Oct;35(4):214–218. doi: 10.1099/00222615-35-4-214. [DOI] [PubMed] [Google Scholar]
  39. Young H. K., Amyes S. G. A new mechanism of plasmid trimethoprim resistance. Characterization of an inducible dihydrofolate reductase. J Biol Chem. 1986 Feb 25;261(6):2503–2505. [PubMed] [Google Scholar]
  40. Young H. K., Amyes S. G. Characterisation of a new transposon-mediated trimethoprim-resistant dihydrofolate reductase. Biochem Pharmacol. 1985 Dec 15;34(24):4334–4337. doi: 10.1016/0006-2952(85)90296-5. [DOI] [PubMed] [Google Scholar]
  41. Young H. K., Skurray R. A., Amyes S. G. Plasmid-mediated trimethoprim-resistance in Staphylococcus aureus. Characterization of the first gram-positive plasmid dihydrofolate reductase (type S1). Biochem J. 1987 Apr 1;243(1):309–312. doi: 10.1042/bj2430309. [DOI] [PMC free article] [PubMed] [Google Scholar]

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