Opinion of the Scientific Panel on Genetically Modified Organisms on the use of antibiotic resistance genes as marker genes in genetically modified plants

EFSA Journal

Volumn 2, Issue 4, 2004, Pages

[No Author Info available]

Author keywords

antibiotic resistance marker genes; antibiotics; Directive 2001 18 EC; environment; GM plants; GMOs; horizontal gene transfer; human health; II gene; safety

Indexed keywords

EID: 85078380356     PISSN: None     EISSN: 18314732     Source Type: Journal    
DOI: 10.2903/j.efsa.2004.48     Document Type: Article

References (67)

1. Beever, D.E. and Kemp, C.F., 2000. Safety issues associated with the DNA in animal feed derived from genetically modified crops. A review of scientific and regulatory procedures. Nutr. Abstr. Rev.Series B: Livestock Feeds and Feeding, 70, 175–182.
2. Bennett, P. M., Livesey, C. T., Nathwani, D., Reeves, D. S., Saunders, J. R. and Wise, R., 2004. An assessment of the risks associated with the use of antibiotic resistance genes in genetically modified plants: report of the Working Party of the British Society for Antimicrobial Chemotherapy. J. Antimicrob. Chemother., 53, 418–431. jac.oupjournals.org/cgi/reprint/53/3/418.pdf.
3. Bermudes, H., Jude, F. C. Arpin, C. Quentin, Morand, A. and Labia, R., 1997. Characterization of an inhibitor-resistant TEM (IRT) ß-lactamase in a novel strain of Klebsiella pneumoniae. Antimicrob. Agents Chemother., 41, 222.
4. Bryan, L.E., 1984. In: Antimicrobial Drug Resistance, Bryan, L.E. ed. (Academic, New York), 241–277.
5. Bush, K., Jacoby, G.A. and Medeiros, A.A., 1995. A functional classification scheme for ß-lactamases and its correlation with molecular structure. Antimicrob. Agents Chemother., 39, 1211–1233.
6. Chambers, P.A., Duggan, P.S., Heritage, J. and Forbes, J.M., 2002. The fate of antibiotic resistance marker genes in transgenic plant feed material fed to chickens. J. Antimicrobial Chemotherapy, 49, 161–164.
7. Chen, I. and Dubnau, D., 2003. DNA transport during transformation. Frontiers in Bioscience, 8, 544–556.
8. Courvalin, P. and Carlier, C., 1981. Resistance towards aminoglycoside-aminocyclitol antibiotics in bacteria. J. Antimicrob. Chemother., 8, 57–69.
9. DANMAP, 1997. Danish Integrated Antimicrobial Resistance Monitoring and Research Programme. Consumption of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, foods and humans in Denmark, Danish Zoonosis Institute, Danish Veterinary Institute, Copenhagen. www.dfvf.dk/Files/Filer/Zoonosecentret/Publikationer/Danmap/Danmap_1997.pdf.
10. DANMAP, 2001. Danish Integrated Antimicrobial Resistance Monitoring and Research Programme. Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, food and humans in Denmark, Danish Zoonosis Institute, Danish Veterinary Institute, Copenhagen. ISSN 1600-2032. www.dfvf.dk/Files/Filer/Zoonosecentret/Publikationer/Danmap/Danmap_2001.pdf.
11. Davies, J. and Smith, D.I., 1978. Plasmid-determined resistance to antimicrobial agents. Annu. Rev. Microbiol., 32, 469–518.
12. De Vries, J., and Wackernagel, W., 1998. Detection of nptII kanamycin resistance genes in genomes of transgenic plants by marker rescue transformation. Mol. and Gen. Genet., 257, 606–613.
13. De Vries, J., Meier, P., and Wackernagel, W., 2001. The natural transformation of the soil bacteria Pseudomonas stutzeri and Acinetobacter sp by transgenic plant DNA strictly depends on homologous sequences in the recipient cells. FEMS Microbiol Lett., 195, 211–215.
14. Duggan, P.S., Chambers, P.A., Heritage, J., and Forbes, J.M., 2000. Survival of free DNA encoding antibiotic resistance from transgenic maize and the transformation activity of DNA in ovine saliva, ovine rumen fluid and silage effluent. FEMS Microbiology Lett., 191, 71–77.
15. Duggan, P.S., Chambers P.A., Heritage, J. and Forbes, J.M., 2003. Fate of genetically modified maize DNA in the oral cavity and rumen of sheep. British J Nutrition, 89, 159–166.
16. EC, 2001. Directive 2001/18/EC of the European Parliament and of the Council of 12 March 2001 on the deliberate release into the environment of genetically modified organisms and repealing Council Directive 90/220/EEC. Official Journal of the European Communities, L106, 1–39. europa.eu.int/eur-lex/pri/en/oj/dat/2001/l_106/l_10620010417en00010038.pdf.
17. Einspanier, R., Klotz, A., Kraft, J., Aulrich., K., Poser, R., Schwagele, F., Jahreis, G. and Flachowsky, G., 2001. The fate of forage plant DNA in farm animals: a collaborative case study investigating cattle and chicken fed recombinant plant material. European Food Research and Technology, 212, 129–134.
18. Fuchs, R.L., Heeren, R.A., Gustafson, M.E., Rogan, G.J., Bartnicki, D.E., Leimgruber, R.M., Finn, R.F., Hershman, A. and Berberich, S.A., 1993a. Purification and characterization of microbially expressed neomycin phosphotransferase II (NPTII) protein and its equivalence to the plant expressed protein. Bio/Technology, 11, 1537–1542.
19. Fuchs, R.L., Ream, J.E., Hammond, B.G., Naylor, M.W., Leimgruber, R.M. and Berberich, S.A., 1993b. Safety assessment of the neomycin phosphotransferase-II (NPTII) protein. Bio/Technology, 11, 1543–1547.
20. Garfinkel, D.J., Simpson, R.B., Ream, L.W., White, F.F., Gordon, M.P. and Nester, E.W., 1981. Genetic analysis of crown gall; fine structure map of the T-DNA by site-directed mutagenesis. Cell, 27, 143–153.
21. Gebhard. F. and Smalla. K. 1998. Transformation of Acinetobacter sp. strain BD413 by transgenic sugar beet DNA. Applied and Environmental Microbiology, 64(4), 1550–1554. 261.
22. Gritz, L. and Davies, J., 1983. Plasmid-encoded hygromycin B resistance: the sequence of hygromycin B phosphotransferase gene and its expression in Escherichia coli and Saccharomyces cerevisiae. Gene, 25, 179–188.
23. Heuer, H., Krögerrecklenfort, E., Egan, S., van Overbeek, L., Guillaume, G., Nikolakopoulou, T.L., Wellington, E.M.H., van Elsas, J.D., Collard, J.-M., Karagouni, A.D. and Smalla, K., 2002. Gentamicin resistance genes in environmental bacteria: prevalence and transfer. FEMS Microbiol. Ecol., 42, 289–302.
24. Heym, B., Honoré, N., Truffot-Pernot, C., Banerjee, A., Schurra, C., Jacobs, W.R., Jr., van Embden, J.D.A., Grosset, J.H. and Cole, S.T., 1994. Implications of multidrug resistance for the future of short-course chemotherapy of tuberculosis: a molecular study. Lancet 344, 293–298.
25. Hinton, M., Kaukas, A. and Linton, A.H., 1986. The ecology of drug resistance in enteric bacteria. J. Appl. Bacteriol. Symp. Suppl. 1986, 77S–92S.
26. Hohlweg, U. and Doerfler, W., 2001. On the fate of plant or other foreign genes upon the uptake in food or after intramuscular injection in mice. Mol. Gen. Genet., 265, 225–233.
27. Hollingshead, S. and Vapnek, D., 1985. Nucleotide sequence analysis of a gene encoding a streptomycin/spectinomycin adenyltransferase. Plasmid, 13, 17–30.
28. Kay, E., Vogel, T.M., Bertolla, F., Nalin, R. and Simonet P., 2002. In situ transfer of antibiotic resistance genes from transgenic (transplastomic) tobacco plants to bacteria. Appl. Environ. Microbiol., 68, 3345–3351.
29. Klein, J., Altenbuchter, J. and Mattes, R., 1998. Nucleic acid and protein elimination during the sugar manufacturing process of conventional and transgenic sugar beets. J. Biotechnology, 60, 145–153.
30. Klotz, A., and Einspanier, R, 1998. Nachweis von “Novel-Feed” im Tier? Beeintrachtigung des Verbrauchers von Fleish oder Milch ist nicht zu erwarten. Detection of “novel feed” in animals? Injury of consumers of meat or milk is not expected. Mais, 3, 109–111.
31. Kocabiyik, D. and Perlin, M.H., 1992. Altered substrate specificity by substitutions at Tyr218 in bacterial aminoglycoside 3′-phosphotransferase-II. FEMS Microbiol. Lett. 72, 619–624.
32. Kresken, M., Hafner, D. and von Rosenstiel, N., 1999. Zeitliche Entwicklung der Antibiotikaresistenz bei klinisch wichtigen Bakterienspecies in Mitteleuropa. Bundesgesundheitsblatt, 42, 17–25.
33. Kuhstoss, S., and Rao, R.N., 1983. Expression in Streptomyces ambofaciens of an Escherichia coli K-12 gene which confers resistance to hygromycin B. Gene 26(2–3), 295–9.
34. Leboul, J., Davies, J., 1982. Enzymatic modification of hygromycin B in Streptomyces hygroscopicus. J Antibiot., 35(4), 527–528.
35. Leff, L. G., Dana, J. R., McArthur, J. V. and Shimkets, L. J., 1993. Detection of Tn5-like sequences in kanamycin-resistant stream bacteria and environmental DNA. Appl. Environ. Microbiol., 59, 417–421.
36. Leistevuo, T., Leistevuo, J., Österblad, M. et al., 1996. Antimicrobial resistance of fecal aerobic gram-negative bacilli in different age groups in community. Antimicrob. Agents Chemother., 40, 1931–1934.
37. Lewin, B., 2000. Genes VII. Oxford University Press, Oxford, UK.
38. Livermore, D. M., 1995. ß-lactamases in laboratory and clinical resistance. Clin. Microbiol. Rev., 8, 557–584.
39. Lorenz, M.G., and Wackernagel, W., 1994. Bacterial gene transfer by natural genetic transformation in the environment. Microbiological Reviews, 58, 563–602.
40. Maliga, P., Svab, Z., Harper, E. C. and Jones J. D. G., 1988. Improved expression of streptomycin resistance in plants due to a deletion in the streptomycin phosphotransferase coding sequence. Mol. Gen. Genet., 214, 456–459.
41. Malpartida, F., Zalacain, M., Jimenen, A. and Davies, J., 1983. Molecular cloning and expression in Streptomyces lividans of a hygromycin B phosphotransferase gene from Streptomyces hygroscopicus. Biochem Biophys Res Commun, 117, 6–12.
42. Martin-Orue, S.M., O'Donnell, A.G., Arino, J., Netherwood, T., Gilbert H.J. and Mathers J.C., 2002. Degradation of transgenic DNA from genetically modified soya and maize in human intestinal simulations. British Journal of Nutrition, 87, 533–542.
43. Mercer, D.K., Scott, K.P., Bruce-Johnson, W.A., Glover, L.A. and Flint, H.J., 1999. Fate of free DNA and transformation of the oral bacterium Streptococcus gordonii DL1 by plasmid DNA in human saliva. Applied and Environmental Microbiology, 65, 6–10.
44. Mercer, D.K., Scott, K.P., Melville, C.M., Glover, L.A. and Flint, H.J., 2001. Transformation of an oral bacterium via chromosomal integration of free DNA in the presence of human saliva. FEMS Microbiology Letters, 200, 163–167.
45. Nap, J.P., Bijvoet, J. and Stikema, W.J., 1992. Biosafety of kanamycin-resistant transgenic plants: an overview. Transgenic Res., 1, 239–249.
46. Netherwood, T., Martin-Orue, S.M., O'Donnell, A.G., Gockling, S., Gilbert, H. and Mathers, J., 2002. Transgenes in genetically modified soya survive passage through the human small bowel but are completely degraded in the colon. In: Technical report on FSA project ‘Evaluating the risks associated with using GMOs in human foods’, 20–31. www.food.gov.uk/multimedia/pdfs/gmnewcastlereport.PDF.
47. Nielsen, K.M., Bones, A.M., Smalla, K. and Van Elsas, J.D., 1998. Horizontal gene transfer from plants to terrestrial bacteria – A rare event? FEMS Microbiol. Rev., 22, 79–103.
48. Nielsen, K.M., Van Elsas, J.D. and Smalla, K., 2000. Transformation of Acinetobacter sp. strain BD413 (pFG4deltanptII) with transgenic plant DNA in soil microcosms and effects of kanamycin on selection of transformants. Appl. Environ. Microbiol., 66, 1237–1242.
49. Perlin, M.H., and Lerner, S.A., 1986. High-level amikacin resistance in Escherichia coli due to phosphorylation and impaired aminoglycoside uptake. Antimicrob Agents Chemother., 29, 216–24.
50. Proctor, G.N. and Rownd, R.H., 1982. Rosanilins: indicator dyes for chloramphenicol-resistant enterobacteria containing chloramphenicol acetyltransferase. J. Bacteriol., 150, 1375–1382.
51. Rao, R.N., Allen, N.E., Hobbs, J.N., Alborn, W. E., Kirst, H.A., and Paschal, J.W., 1983. Genetic and enzymatic basis of hygromycin B resistance in Escherichia coli. Antimicro. Agents Chemother., 24, 689–695.
52. Redenbaugh, K., Berner, T., Emlay, D., Frankos, B., Hiatt, W., Houck, C., Kramer, M., Malyj, L., Martineau, B., Rachman, N., Rudenko, L., Sanders, R., Sheehy, R. and Wixtrom, R., 1993. Regulatory issues for commercialization of tomatoes with an antisense polygalacturonase gene. In Vitro Cell. Dev. Biol., 29P, 17–26.
53. Redenbaugh, K., Hiatt, W., Martineau, B., Lindemann, J. and Emlay, D., 1994. Aminoglycoside 3′-phosphotransferase II (APH(3′)II): Review of its safety and use in the production of genetically engineered plants. Food Biotechnol., 8, 137–165.
54. Salyers, A., 1996. The real threat from antibiotics. Nature, 384, 304.
55. Sanders, C. and Sanders, W.E., 1992. β-Lactam resistance in gram-negative bacteria: global trends and clinical impact. Clin. Infect. Dis., 15, 824–839.
56. Schlüter, K., Fütterer, J., Potrykus, I., 1995. Horizontal. gene transfer from a transgenic potato line to a bacterial pathogen (Erwinia chrysanthemi) occurs if at all at an extremely low frequency. Biotechnology, 13, 1094–1098.
57. Schmitz, F.J., Fluit, A.C., Gondolf, M., Beyrau, R., Lindenlauf, E., Verhoef, J., Heinz, H.P., Jones, M.E., 1999). The prevalence of aminoglycoside resistance and corresponding resistance genes in clinical isolates of staphylococce from 19 European hospitals. J. Antimicrob Chemother., 43, 253–259.
58. Schubbert, R., Hohlweg, U., Renz, D. and Doerfler, W., 1998. On the fate of orally ingested foreign DNA in mice: chromosomal association and placental transmission to the fetus. Mol. Gen. Genet., 259, 569–576.
59. Schubbert, R., Lettmann, C. and Doerfler, W., 1994. Ingested foreign (phage M13) DNA survives transiently in the gastrointestinal tract and enters the bloodstream of mice. Mol. Gen. Genet., 242, 495–504.
60. Schubbert, R., Renz, D., Schmitz, B. and Doerfler, W., 1997. Foreign (M13) DNA ingested by mice reaches peripheral leukocytes, spleen, and liver via the intestinal wall mucosa and can be covalently linked to mouse DNA. Proceedings of the National Academy of Science USA, 94, 961–966.
61. Shaw, K. J., Rather, P. N., Hare, R. S. and Miller, G. H., 1993. Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes. Microbiol. Rev., 57, 138–163.
62. Smalla, K, Van Overbeek, L.S., Pukall, R. and Van Elsas, J.D., 1993. Prevalence of nptII and Tn5 in kanamycin-resistant bacteria from different environments. FEMS Microbiol. Ecol. 13, 47–58.
63. Smalla, K. and van Elsas, J. D., 1996. Monitoring genetically modified organisms and their recombinant DNA in soil environments. In: J. Tomiuk, K. Wöhrmann and A. Sentker (Eds). Transgenic Organisms - Biological and Social Implications. Birkhäuser Verlag, Basel, Switzerland, 127–146.
64. Svab, Z., Harper, E. C., Jones, J. D. G. and Maliga, P., 1990. Aminoglycoside-3′-adenyltransferase confers resistance to streptomycin and spectinomycin in Nicotiana tabacum. Plant Mol. Biol., 14, 197–205.
65. Tomalsky, M.E. and Crosa, J.H., 1987. Tn1331, a novel multiresistant transposon encoding resistance to amikacin and ampicillin in Klebsiella pneumoniae. Antimicrob. Agents Chemother., 31, 1955–1960.
66. Van Overbeek, L.S., Wellington, E.M.H., Egan, S., Smalla, K., Heuer, H., Collard, J.-M., Guillaume, G., Karagouni, A., Nikolakopoulou, T.L., and van Elsas, J.D., 2002. Prevalence of streptomycin resistance genes in bacterial populations in European habitats. FEMS Microbiol Ecol., 42, 277–288.
67. Waldron, C., Murphy, E. B., Roberts, J. L., Gustafson, G. D., Armour, S. L. and Malcom, S. K., 1985. Resistance to hygromycin B – a new marker for plant transformation studies. Plant Mol. Biol., 5, 103–108.