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Assessment of the Risks of Transferring Antibiotic Resistance Determinants from Transgenic Plants to Micro-organisms

Institutions
University of Leeds, CAS/ LIBA
Start date
1998
End date
2001
Objective
This research project assessed the risks of transferring antibiotic resistance from transgenic plants to micro-organisms and found them to be low.

In essence, this project sought evidence for the occurrence of a very rare event. In order to tackle this problem, a critical step analysis was undertaken. This project was designed to address six main areas of concern.

The research approaches identified at the the start of the project are summarised below:

1) What is the risk that the bla gene will "loop out" from transgenic plant cells? The DNA cassette inserted into the maize plant should be stably incorporated. If, however, it can "loop-out" from the plant DNA, its chances of spreading will be enhanced.

2) Do animals fed on transgenic maize release the bla gene from plants? In order to transfer from GM plant tissues into microbes, it is necessary that the digestion processes release DNA in a form that can be taken up and also be expressed in bacteria. Sheep were used as the model ruminant animal; chickens were used as the non-ruminant. Both chickens and sheep may be fed significant quantities of maize or maize products.

3) With what efficiency can gut organisms take up and express the bla gene? The demonstration that the antibiotic resistance marker gene is digested in the same way as other plant DNA, and that it is thus unavailable for uptake and expression by bacteria in the lower intestine, rendered this question of lesser importance than at the outset of the project.

4) Can the bla gene be mobilised from bacteria within an animal gut? The transfer of blaTEM from GM plant material to microbes in the animal gut, were it to happen, is the first step in spreading this gene to new hosts. In theory, once one bacterium has acquired blaTEM, it may be transferable to other bacteria in the gut environment.

5) Does ensilage of transgenic maize result in the release of the bla gene? Much of the maize feed in the United Kingdom is presented in the form of silage. To make silage, fresh plant material is fermented in the absence of air. Microbes associated with the fresh crop cause the production of organic acids, which preserve the plant material in a form that animals find desirable. The bacteria responsible for the later stages of silage production are fed to animals as part of the silage product. These have the potential to take up and express resistance genes, such as blaTEM found in the maize that is the subject of this study.

6) To what extent does the bla gene undergo mutation to extended spectrum activity in the gut environment? Over the past 15 years, hospitals have seen the emergence of bacteria that are resistant to important first-line antibiotics. This resistance may arise from the mutation of blaTEM, causing substitution of different amino acids in the enzyme that confers resistance to antibiotics. About 90 such mutations have now been described in blaTEM. Many of these allow the enzyme to confer resistance on a much broader spectrum of antibiotics than the original enzyme.

More information
In the production of genetically modified (GM) plants, genes conferring 'desirable' traits are identified and are then assembled in bacteria before delivery into the target plants.

The assembly of genes in bacteria is made simple by including antibiotic resistance marker genes. The presence of a gene that codes for resistance to an antibiotic in a single bacterial cell means that, by adding the appropriate antibiotic to a culture, the single cell can be isolated from millions or even billions of bacteria lacking the resistance gene present in the same culture.

By linking a gene that confers antibiotic resistance on its host bacterium to the genes that are to be inserted into plants, sufficient quantities of DNA can be harvested from a bacterial culture to allow the novel DNA to be delivered easily to the plant.

One marker gene commonly used in the early days of GM crop development, called blaTEM, confers resistance to antibiotics such as ampicillin and amoxycillin.

This gene causes the production of an enzyme, known as a beta-lactamase, which breaks down the structure of these antibiotics, rendering them ineffective against bacteria.

Although the bacteria that live in animal and human guts frequently carry blaTEM, which occurs naturally at a high frequency, this project is designed to examine the risk that blaTEM from GM maize can pass from the modified plant tissues into microbes in animals that are fed GM maize.

Find more about this project and other FSA food safety-related projects at the Food Standards Agency Research webpage.

Funding Source
Food Standards Agency
Project number
G01010
Categories
Antimicrobial Resistance
Bacterial Pathogens
Commodities
Meat, Poultry, Game