Antibiotic resistance genes in genetically modified microorganisms

There are no indications that our use of antibiotic resistance genes has led to an increase in antibiotic resistance in the environment. However, we have decided to find alternative methods in future developments of new enzyme production strains.

Antibiotic is a generic name for substances used in the treatment of human infections caused by microorganisms. The function of the antibiotics is to kill the microorganisms causing the infections. Well-known examples are the penicillins.
 

Antibiotic resistance

If a microorganism is resistant towards a certain antibiotic, it will survive although it is treated with the antibiotic. Resistance occurs when the microorganism has a gene coding for a protein which makes it resistant towards antibiotics.
 
The antibiotic resistance genes exist in nature in microorganisms. Via natural gene transfer a microorganism can acquire the resistance gene which makes it resistant to an antibiotic. Future generations of this microorganism will then also benefit from the resistance gene since the resistance is hereditary.
 
Most antibiotics used in the treatment of human infections will, after a few years' use, tend to meet the occasional strain of microorganism which is not susceptible to their effects. This is why antibiotics are regularly replaced by new ones in the treatment of human diseases.
 

An important tool in the biotech era

From the beginning of the modern biotech era, the use of antibiotic resistance genes has been an important tool in the development of genetically modified plants or microorganisms. The antibiotic resistance genes are used as markers in the construction and development phase of a recombinant organism, because they can identify a recombinant organism which has taken up the genes in the intended way.
 
The antibiotic resistance gene is always transferred together with the gene transferred deliberately. In this way the presence of the desired gene can easily be detected in the receiving cell by means of a simple test: The modified organism is grown in the presence of the relevant ant ibiotic. If the modified organism survives, it means that it has received the antibiotic resistance gene (= the marker), and the transfer of the desired gene has been successful.
 

Research in risk

Over the past decade, researchers have investigated if antibiotic resistance genes used in the transfer of the desired modification of a plant or a microorganism could then be transferred to microorganisms which are harmful to humans. If so, these microorganisms would be resistant to the antibiotic.
 
So far, the research shows that this is very unlikely to happen in nature.
Over the last years, however, there has been a growing concern about the widespread use of antibiotics in human and veterinary applications. This has lead to an increased frequency of bacterial resistance to antibiotics.
 

Novozymes' position on the use of antibiotic resistance genes

Novozymes has been using antibiotic resistance gene markers in the construction of genetically modified microorganisms for the production of industrial enzymes since the start of the modern biotech era.
 
All the genetically modified microorganisms that we use as production strains have been safety evaluated and approved before being used in production.
 
In the development of our constructions we have secured that the possibility of gene transfer has been minimised, and our monitoring programmes give no indications that this use of antibiotic resistance genes has led to an increase in antibiotic resistance in the environment.
 
Novozymes agrees that the increased frequency of bacterial resistance to antibiotics gives rise to general concern. We also agree that it is important that all efforts are made to limit this increase.
 
Although the risk of an increase in antibiotic resistance as a result of our use of antibiotic resistance marker genes is extremely small, Novozymes has therefore decided to find alternative ways of obtaining selection markers in future developments of new enzyme production strains.