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. 1991 Sep;35(9):1840–1848. doi: 10.1128/aac.35.9.1840

Genetic analyses of sulfonamide resistance and its dissemination in gram-negative bacteria illustrate new aspects of R plasmid evolution.

P Rådström 1, G Swedberg 1, O Sköld 1
PMCID: PMC245278  PMID: 1952855

Abstract

In contrast to what has been observed for many other antibiotic resistance mechanisms, there are only two known genes encoding plasmid-borne sulfonamide resistance. Both genes, sulI and sulII, encode a drug-resistant dihydropteroate synthase enzyme. In members of the family Enterobacteriaceae isolated from several worldwide sources, plasmid-mediated resistance to sulfonamides could be identified by colony hybridization as being encoded by sulI, sulII, or both. The sulI gene was in all cases found to be located in the newly defined, mobile genetic element, recently named an integron, which has been shown to contain a site-specific recombination system for the integration of various antibiotic resistance genes. The sulII gene was almost exclusively found as part of a variable resistance region on small, nonconjugative plasmids. Colony hybridization to an intragenic probe, restriction enzyme digestion, and nucleotide sequence analysis of small plasmids indicated that the sulII gene and contiguous sequences represent an independently occurring region disseminated in the bacterial population. The sulII resistance region was bordered by direct repeats, which in some plasmids were totally or partially deleted. The prevalence of sulI and sulII could thus be accounted for by their stable integration in transposons and in plasmids that are widely disseminated among gram-negative bacteria.

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  1. AKIBA T., KOYAMA K., ISHIKI Y., KIMURA S., FUKUSHIMA T. On the mechanism of the development of multiple-drug-resistant clones of Shigella. Jpn J Microbiol. 1960 Apr;4:219–227. doi: 10.1111/j.1348-0421.1960.tb00170.x. [DOI] [PubMed] [Google Scholar]
  2. Albritton W. L., Brunton J. L., Slaney L., MacLean I. Plasmid-mediated sulfonamide resistance in Haemophilus ducreyi. Antimicrob Agents Chemother. 1982 Jan;21(1):159–165. doi: 10.1128/aac.21.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BERTANI G. Studies on lysogenesis. I. The mode of phage liberation by lysogenic Escherichia coli. J Bacteriol. 1951 Sep;62(3):293–300. doi: 10.1128/jb.62.3.293-300.1951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bachmann B. J. Pedigrees of some mutant strains of Escherichia coli K-12. Bacteriol Rev. 1972 Dec;36(4):525–557. doi: 10.1128/br.36.4.525-557.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barth P. T., Grinter N. J. Comparison of the deoxyribonucleic acid molecular weights and homologies of plasmids conferring linked resistance to streptomycin and sulfonamides. J Bacteriol. 1974 Nov;120(2):618–630. doi: 10.1128/jb.120.2.618-630.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brown N. L., Misra T. K., Winnie J. N., Schmidt A., Seiff M., Silver S. The nucleotide sequence of the mercuric resistance operons of plasmid R100 and transposon Tn501: further evidence for mer genes which enhance the activity of the mercuric ion detoxification system. Mol Gen Genet. 1986 Jan;202(1):143–151. doi: 10.1007/BF00330531. [DOI] [PubMed] [Google Scholar]
  7. Cameron F. H., Groot Obbink D. J., Ackerman V. P., Hall R. M. Nucleotide sequence of the AAD(2'') aminoglycoside adenylyltransferase determinant aadB. Evolutionary relationship of this region with those surrounding aadA in R538-1 and dhfrII in R388. Nucleic Acids Res. 1986 Nov 11;14(21):8625–8635. doi: 10.1093/nar/14.21.8625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dale J. W., Godwin D., Mossakowska D., Stephenson P., Wall S. Sequence of the OXA2 beta-lactamase: comparison with other penicillin-reactive enzymes. FEBS Lett. 1985 Oct 21;191(1):39–44. doi: 10.1016/0014-5793(85)80989-3. [DOI] [PubMed] [Google Scholar]
  9. Derbyshire K. M., Hatfull G., Willetts N. Mobilization of the non-conjugative plasmid RSF1010: a genetic and DNA sequence analysis of the mobilization region. Mol Gen Genet. 1987 Jan;206(1):161–168. doi: 10.1007/BF00326552. [DOI] [PubMed] [Google Scholar]
  10. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [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. Grinter N. J., Barth P. T. Characterization of SmSu plasmids by restriction endonuclease cleavage and compatibility testing. J Bacteriol. 1976 Oct;128(1):394–400. doi: 10.1128/jb.128.1.394-400.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Guerry P., van Embden J., Falkow S. Molecular nature of two nonconjugative plasmids carrying drug resistance genes. J Bacteriol. 1974 Feb;117(2):619–630. doi: 10.1128/jb.117.2.619-630.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Harley C. B., Reynolds R. P. Analysis of E. coli promoter sequences. Nucleic Acids Res. 1987 Mar 11;15(5):2343–2361. doi: 10.1093/nar/15.5.2343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hollingshead S., Vapnek D. Nucleotide sequence analysis of a gene encoding a streptomycin/spectinomycin adenylyltransferase. Plasmid. 1985 Jan;13(1):17–30. doi: 10.1016/0147-619x(85)90052-6. [DOI] [PubMed] [Google Scholar]
  16. Hughes V. M., Datta N. Conjugative plasmids in bacteria of the 'pre-antibiotic' era. Nature. 1983 Apr 21;302(5910):725–726. doi: 10.1038/302725a0. [DOI] [PubMed] [Google Scholar]
  17. Huovinen P., Huovinen S., Jacoby G. A. Sequence of PSE-2 beta-lactamase. Antimicrob Agents Chemother. 1988 Jan;32(1):134–136. doi: 10.1128/aac.32.1.134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kawabe H., Tanaka T., Mitsuhashi S. Streptomycin and Spectinomycin resistance mediated by plasmids. Antimicrob Agents Chemother. 1978 Jun;13(6):1031–1035. doi: 10.1128/aac.13.6.1031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Korfmann G., Lüdtke W., van Treeck U., Wiedemann B. Dissemination of streptomycin and sulfonamide resistance by plasmid pBP1 in Escherichia coli. Eur J Clin Microbiol. 1983 Oct;2(5):463–468. doi: 10.1007/BF02013905. [DOI] [PubMed] [Google Scholar]
  20. Lawn A. M., Meynell G. G., Meynell E., Datta N. Sex pili and the classification of sex factors in the enterobacteriaceae. Nature. 1967 Oct 28;216(5113):343–346. doi: 10.1038/216343a0. [DOI] [PubMed] [Google Scholar]
  21. Martin C., Timm J., Rauzier J., Gomez-Lus R., Davies J., Gicquel B. Transposition of an antibiotic resistance element in mycobacteria. Nature. 1990 Jun 21;345(6277):739–743. doi: 10.1038/345739a0. [DOI] [PubMed] [Google Scholar]
  22. Martinez E., de la Cruz F. Genetic elements involved in Tn21 site-specific integration, a novel mechanism for the dissemination of antibiotic resistance genes. EMBO J. 1990 Apr;9(4):1275–1281. doi: 10.1002/j.1460-2075.1990.tb08236.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Müller-Hill B., Crapo L., Gilbert W. Mutants that make more lac repressor. Proc Natl Acad Sci U S A. 1968 Apr;59(4):1259–1264. doi: 10.1073/pnas.59.4.1259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. NAKAYA R., NAKAMURA A., MURATA Y. Resistance transfer agents in Shigella. Biochem Biophys Res Commun. 1960 Dec;3:654–659. doi: 10.1016/0006-291x(60)90081-4. [DOI] [PubMed] [Google Scholar]
  25. Ouellette M., Bissonnette L., Roy P. H. Precise insertion of antibiotic resistance determinants into Tn21-like transposons: nucleotide sequence of the OXA-1 beta-lactamase gene. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7378–7382. doi: 10.1073/pnas.84.21.7378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ouellette M., Roy P. H. Homology of ORFs from Tn2603 and from R46 to site-specific recombinases. Nucleic Acids Res. 1987 Dec 10;15(23):10055–10055. doi: 10.1093/nar/15.23.10055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rådström P., Swedberg G. RSF1010 and a conjugative plasmid contain sulII, one of two known genes for plasmid-borne sulfonamide resistance dihydropteroate synthase. Antimicrob Agents Chemother. 1988 Nov;32(11):1684–1692. doi: 10.1128/aac.32.11.1684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Scholz P., Haring V., Wittmann-Liebold B., Ashman K., Bagdasarian M., Scherzinger E. Complete nucleotide sequence and gene organization of the broad-host-range plasmid RSF1010. Gene. 1989 Feb 20;75(2):271–288. doi: 10.1016/0378-1119(89)90273-4. [DOI] [PubMed] [Google Scholar]
  30. Sköld O. R-factor-mediated resistance to sulfonamides by a plasmid-borne, drug-resistant dihydropteroate synthase. Antimicrob Agents Chemother. 1976 Jan;9(1):49–54. doi: 10.1128/aac.9.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Stokes H. W., Hall R. M. A novel family of potentially mobile DNA elements encoding site-specific gene-integration functions: integrons. Mol Microbiol. 1989 Dec;3(12):1669–1683. doi: 10.1111/j.1365-2958.1989.tb00153.x. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. 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]
  34. Swedberg G. Organization of two sulfonamide resistance genes on plasmids of gram-negative bacteria. Antimicrob Agents Chemother. 1987 Feb;31(2):306–311. doi: 10.1128/aac.31.2.306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Swedberg G., Sköld O. Characterization of different plasmid-borne dihydropteroate synthases mediating bacterial resistance to sulfonamides. J Bacteriol. 1980 Apr;142(1):1–7. doi: 10.1128/jb.142.1.1-7.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Swedberg G., Sköld O. Plasmid-borne sulfonamide resistance determinants studied by restriction enzyme analysis. J Bacteriol. 1983 Mar;153(3):1228–1237. doi: 10.1128/jb.153.3.1228-1237.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Swift G., McCarthy B. J., Heffron F. DNA sequence of a plasmid-encoded dihydrofolate reductase. Mol Gen Genet. 1981;181(4):441–447. doi: 10.1007/BF00428733. [DOI] [PubMed] [Google Scholar]
  38. Tait R. C., Rempel H., Rodriguez R. L., Kado C. I. The aminoglycoside-resistance operon of the plasmid pSa: nucleotide sequence of the streptomycin-spectinomycin resistance gene. Gene. 1985;36(1-2):97–104. doi: 10.1016/0378-1119(85)90073-3. [DOI] [PubMed] [Google Scholar]
  39. Tenover F. C., Phillips K. L., Gilbert T., Lockhart P., O'Hara P. J., Plorde J. J. Development of a DNA probe from the deoxyribonucleotide sequence of a 3-N-aminoglycoside acetyltransferase [AAC(3)-I] resistance gene. Antimicrob Agents Chemother. 1989 Apr;33(4):551–559. doi: 10.1128/aac.33.4.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Tran van Nhieu G., Collatz E. Primary structure of an aminoglycoside 6'-N-acetyltransferase AAC(6')-4, fused in vivo with the signal peptide of the Tn3-encoded beta-lactamase. J Bacteriol. 1987 Dec;169(12):5708–5714. doi: 10.1128/jb.169.12.5708-5714.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Willson P. J., Albritton W. L., Slaney L., Setlow J. K. Characterization of a multiple antibiotic resistance plasmid from Haemophilus ducreyi. Antimicrob Agents Chemother. 1989 Sep;33(9):1627–1630. doi: 10.1128/aac.33.9.1627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Willson P. J., Deneer H. G., Potter A., Albritton W. Characterization of a streptomycin-sulfonamide resistance plasmid from Actinobacillus pleuropneumoniae. Antimicrob Agents Chemother. 1989 Feb;33(2):235–238. doi: 10.1128/aac.33.2.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wise E. M., Jr, Abou-Donia M. M. Sulfonamide resistance mechanism in Escherichia coli: R plasmids can determine sulfonamide-resistant dihydropteroate synthases. Proc Natl Acad Sci U S A. 1975 Jul;72(7):2621–2625. doi: 10.1073/pnas.72.7.2621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wohlleben W., Arnold W., Bissonnette L., Pelletier A., Tanguay A., Roy P. H., Gamboa G. C., Barry G. F., Aubert E., Davies J. On the evolution of Tn21-like multiresistance transposons: sequence analysis of the gene (aacC1) for gentamicin acetyltransferase-3-I(AAC(3)-I), another member of the Tn21-based expression cassette. Mol Gen Genet. 1989 Jun;217(2-3):202–208. doi: 10.1007/BF02464882. [DOI] [PubMed] [Google Scholar]
  45. Womble D. D., Rownd R. H. Genetic and physical map of plasmid NR1: comparison with other IncFII antibiotic resistance plasmids. Microbiol Rev. 1988 Dec;52(4):433–451. doi: 10.1128/mr.52.4.433-451.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]
  47. Zolg J. W., Hänggi U. J. Characterization of a R plasmid-associated, trimethoprim-resistant dihydrofolate reductase and determination of the nucleotide sequence of the reductase gene. Nucleic Acids Res. 1981 Feb 11;9(3):697–710. doi: 10.1093/nar/9.3.697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. van Treeck U., Schmidt F., Wiedemann B. Molecular nature of a streptomycin and sulfonamide resistance plasmid (pBP1) prevalent in clinical Escherichia coli strains and integration of an ampicillin resistance transposon (TnA). Antimicrob Agents Chemother. 1981 Mar;19(3):371–380. doi: 10.1128/aac.19.3.371. [DOI] [PMC free article] [PubMed] [Google Scholar]

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