Kanamycin Still Used and Cross-Reacts with New Antibiotics

Kanamycin resistance genes are approved as selectable markers on grounds that the antibiotic is no longer in use. Prof. Joe Cummins reports that on the contrary, kanamycin is still in use and that cross-reaction between kanamycin and other related antibiotics is commonplace.

The antibiotic kanamycin is used extensively in crop genetic engineering as a selectable marker. A selectable marker is a gene inserted into a cell or organism to allow the modified form to be selectively amplified while unmodified organisms are eliminated. In crop genetic engineering the selectable marker is used in the laboratory to identify cells or embryos that bear the genetic modifications that the engineer wishes to commercialize. The selection gene is used once briefly in the laboratory but thereafter the genetically modified (GM) crop has the unused marker gene in each and every one of its cells.

There is a well known cross resistance between antibiotics of a particular type. A mutation to resistance to an antibiotic may cause resistance to some or all of the members of the antibiotic family [1]. Kanamycin is a member of the family aminoglycoside antibiotics. Cross resistance between Kanamycin and other aminoglycosides including streptomycin, gentamycin and tobramycin was found to vary markedly between isolates. All of the antibiotics mentioned are used to treat human diseases. The aminoglycoside antibiotic neomycin was found to cross react with kanamycin B in inhibiting RNase P ribozyme 16s ribosomal RNA and tRNA maturation [2].

Along with cross resistance to aminoglycoside antibiotics, pathogenic bacteria frequently develop multiple drug resistance transmitted on a single plasmid. For example, the cholera pathogen Vibrio cholerae, first isolated from India, Bangladesh and Thailand [3], was found to have a plasmid resistant to tetracycline, ampicillin, chloramphenicol, kanamycin, gentamycin, sulphaethoazole and trimethoprim. Pathogenic bacteria do aquire plasmids with multiple antibiotic resistance genes in areas where the antibiotics are used extensively.

In spite of the belief of many genetic engineers that kanamycin is no longer employed in medical applications, there is evidence that the antibiotic is used extensively in North America where crops bearing kanamycin resistance are marketed without warning labels. Kanamycin is used prior to endoscopy of colon and rectum [4] and to treat ocular infections [5]. It is used in blunt trauma emergency treatment [6] and has been found to be effective against E coli 0157 without causing release of verotoxin [7].

In conclusion, extensive use of kanamycin resistance marker genes in genetically modified crops is unjustifiable in the face of current medical applications.

Article first published 27/05/01

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References

1. Onaolapo J. Cross-resistance between some aminoglycoside antibiotics. Afr J Med Sci . 1994, 23,215-9.
2. Mikkelsen N, Brannvali M, Virtanen A and Kirsebom L. Inhibition of P RNA cleavage by aminoglycosides. Proc. Natnl Acad Sci USA, 1999, 96,6155-60.
3. Yamamoto T, Nair G and Takeda Y. Emergence of tetracycline resistance due to a multiple drug resistance plasmid in Vibrio cholerae 0139. FEMS Immunol Med Microbiol 1995, 11,131-6
4. Ishikawa H, Ikuko A, Minami T, Shinmoura Y, Ojo H and Otani T. Prevention of infectious complications subsequent to endoscopic treatment of the colon and rectum. J Infect Chemother, 1999, 5, 86-90
5. Hehl E, Beck R, Luthard K, Guthoff R and Drewelow B. Improved penetration of amonoglycosides and fluoroquininolones into the aqueous humour of patients by means of acuvue contact lenses. Eur J Pharmacol, 1999, 55,317-323.
6. Yelon J, Green J and Evans J. Efficacy of an interperitoneal antibiotic to reduce incidence of infection in the trauma patient a prospective randomized study. J AmCollSurg, 1996, 182,509-14.
7. Ito T, Akino E and Hiramatsu K. Evaluation of antibiotics for enterohemorrhagic Escherichia coli 0157 enteritis effect of various antibiotics on extracellular release of verotoxin. Kansenshogaku Zasshi, 1997, 71,130-5.