• BACTERIA WITH KANAMYCIN RESISTANCE GENES CROSSRESISTANT TO VALUABLE ANTIBIOTICS.
• The proponents for GMO foods have maintained that the Kanamycin resistance marker genes, often used in genetically engineered food, are of no practical importance as Kanamycin is of little use today. But this study reports that marker gene also confers resistance to other antibiotics that are of considerable value.
• OBSERVATIONS INDICATING THAT ANTIBIOTIC RESISTANCE GENE MARKERS MAY CONTRIBUTE TO INCREASED BACTERIAL RESISTANCE TO ANTIBIOTICS
• The proponents for GMO foods have maintained that there are no possibilities for transfer of antibiotics resistance genes from food to bacteria in the gut. An important justification for this opinion has been that DNA is believed to be digested to much smaller pieces than a gene, but no conclusive observations have been delivered that substantiate this assumption. Obervations are presented here that:
  1) indicate that pieces of DNA of the size of genes can survive digestion,
  2) isolated pieces of DNA may be taken up by bacteria,
  3) genes may be transferred between bacteria in the gut.

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Published May 1997

Jaan Suurküla MD

Smirnov VV (1994) et al. Antibiot-Khimiorec Apr; 39(4): 23-28

Onaolapo,J. (1994) Afr.J.MedMedSci 23,215-9 .

For a recent text on this issue, see

"Kanamycin Still Used and Cross-Reacts with New Antibiotics" by professor Joe Cummins (May 2001).

OBSERVATIONS INDICATING THAT ANTIBIOTIC GENE MARKERS MAY CONTRIBUTE TO INCREASED BACTERIAL RESISTANCE TO ANTIBIOTICS

Unsuccessfully treated bacterial infections may cause serious damages to various organs, chronically undermine health and lead to acute death. Many have forgotten that this was a serious threat, killing even young people before the "era of antibiotics" that begun after WW II.

The present situation in the world with an high and increasing prevalence of resistant baceria threatens to abolish the usefulness of antibiotics in the treatment of serious infections. Some experts in this field warn that this may lead us back to the defenseless situation of the preantibiotic area. An additional problem is that there has recently occurred transfer of virulence genes between different bacteria. Such genes make the bacteria more contagious and invasive. Ho et al found reasons to suspect that the use of special, so called vector genes , used in GE organisms to ensure gene insertion insertion, may considerably increase such gene transfer. They warn that this may already have lead to the emergence of new and harmful bacteria such as the Escherichia Coli 0157:H7 that cause life-threatening hemmoragic colitis (see: http://www.psrast.org/hrtrintr.htm.

If so, the problems with bacterial infections might become even worse than in the pre-antibiotic era.

In the end of May 1997 the news was cabled over the world that the first bacterium, that is totally resitant to all known antibiotics, has been detected in Japan. It is a Staphylococcus that may cause very problematic infections.

If not before, it is time now for the authorities in the world to wake up and take resolute measures to reduce the factors that contribute to antibiotics resistance. So far, rather the opposite has been true as FDA, for example, increased the allowed concentration of antiobiotics in cow's milk hundredfold (because the use of recombitant Bovine Growth Hormone caused udder infections) and as in many countries (Sweden is one of the few exceptions) it is allowed to add "cocktails" of different antibiotics to the food to promote the growth of the animals. Also, too weak measures have so far been taken to enforce restrictivity in the prescription of antibiotics by physicians. But all these factors could be rapidly mended through resolute political decisions.

An additional potential source of antibiotic resistance are the antibiotic resistance genes used as markers of successful insertion of a gene in genetic engineerig i.e. of foods. The genes used are most commonly a gene conferring resistance against the aminoglykoside antibiotics and a gene conferring resistance to ampicillin.

If the antibiotic resistance genes can be transmitted from food to bacteria, widespread use of genetically engineered food would be an important additional source of resistance to these important and clinically valuable antibiotics.

There are no studies proving that transfer of resistance genes from genetically engineered food to pathogenic bacteria is not possible.

There are however a number of observations that indicate that this might occur:

1. A research team lead by Walter Doerfler in Cologne, Germany, has repeatedly demonstrated that pieces of DNA, as large as genes, can survive digestion in the gastrointestinal tract (besides, they were absorbed and could be found in the blood and in a later study even transiently in the tissues). (Shubbert R et al. 1994).

2. There are studies showing that especially stressed and starving bacteria are prone to take up pieces of isolated DNA, see the article by Ho and Tappeseer, and e g the following references from this article: Atlas, M., et al (1992). Saunders, J.R. & Saunders, V.A. (1993). Schaefer, A., Kalinowski, J. & P-hler, A. (1994).

3. There are evidence indicating that genes, including antibiotic markers, may be transferred between bacteria as shown in the above mentioned article by Ho and Tappeseer. This includes horizontal gene transfer between gut bacteria in mice and chickens (Doucet-Populaire, F. 1992; Guillot, J.F. & Boucaud, J.L. 1992). (see also the article by Ho and Tappeseer):

In addition to direct transfer, Ho and Tappeseer mention evidence indicating that the possibility of transfer by way of viruses must also be taken into consideration.

CONCLUSION

The above mentioned observations indicate 1) that genes may survive digestion. 2) that isolated pieces of DNA like genes may be taken up by bacteria. 3) that antibiotic marker genes may be transferred between bacteria. This makes it unjustified to dismiss the possibility that genes from the food may be taken up by the normal bacteria that inhabitate the gastrointestinal channel and may be transferred from them to patohgenic bacteria that happen to enter the gut. If so, the result might be an increase in the prevalence of pathogenic bacteria that are resistant to valuable antibiotics.

The antibiotics resistance situation in the world is becoming increasingly serious today. It is expected that in the worst case, epidemics of intractable bacteria may become a reality in nearby future. Therefore it is not acceptable to add an additional factor that may contribute to the "resistance epidemic".

The biotechnology proponents argue that "there are other more important factors contributing to this situation so it is not meaningful to eliminate this one". This argument is untenable as it is possible to drastically reduce all the other factors contributing to resistance increase by adequate measures. But there are reasons to believe that it will not be possible to eliminate the antibiotic resistance genes once they have been introduced into crops. This is because it has been shown experimentally that genetically engineered genes can be transferred from plants to soil bacteria (see "Horizontal transfer - gene transfer without reproduction"). In soil bacteria they may persist indefinitely.

Therefore, it is justified to require positive experimental proof that the presence of antibiotic resistance genes in GE crops and in GE food will not contribute to an increase of the antibiotic resistance problem. Today, no such evidence exists.

Until such studies have been done, considering the seriousness of the "resistance epidemic", it is not responsible to allow widespread usage of crops and foods containing antibiotic resistance genes. This is especially so as the GE products available today are of no significant value to humanity.

The resistance gene problem adds to other potentially serious and and incompletely known risks and problems with genetically engineered foods, such as the unexpected appearance of toxic and allergenic substances that may be difficult to detect even with the best safety assessment methods and the risk for emergence of new viruses ( see "The Virus Hazard").

Jaan Suurküla MD

May 1997. Revised March 1999.


References:

Atlas, M., Bennett, A.M., Colwell, R., Van Elsas, J., Kjelleberg,S., Pedersen,J. & Wacker- Nagel, S. (1992). Persistence and survival of genetically-modified microorganisms released into the environment, p.117, in The Release of Genetically Modified Microorganisms (Eds. D.E.S.
Stewart-Tull and M. Sussman), Plenum Press, New York.

Doucet-Populaire, F. (1992). Conjugal transfer of genetic information in gnotobiotic mice, in Microbial Releases (Ed. M.J. Gauthier), Springer Verlag, Berlin, 345pp.

Guillot, J.F. & Boucaud, J.L. (1992). In vivo transfer of a conjugative plasmid between isogenic Escherichia coli strains in the gut of chickens, in the presence and absence of selective pressure, Pp. 167-174, in Microbial Releases (Ed. M.J. Gauthier), Springer Verlag, Berlin, 345pp.

Saunders, J.R. & Saunders, V.A. (1993). Genotypic and phenotypic methods for the detection of specific released microorganisms, Pp 27-59 in Monitoring Genetically Manipulated Microorganisms in the Environment (Ed. C. Edwards), John Wiley & Sons Ltd.,New York.

Schaefer, A., Kalinowski, J. & P-hler, A. (1994). Increased fertility of Corynebacterium glutamicum recipients in intergeneric matings with Escherichia coli afterstress exposure. Applied and Environmental Microbiology 60: 756-759.

Shubbert R et al. (1994) "Ingested foreign (phage M13) DNA survives transiently in the gastrointestinal tract and enters the bloodstream of mice" Mol Gen Genet 242:495-504.