Gene-edited calves had antibiotic-resistant genes inserted

When the producer of hornless insemination bulls was about to sit back after all the work, others discovered that not everything was as it should be with the genetically edited calves. The company that produced hornless cattle had inserted too much DNA. They did this with the TALEN method which, like the CRISPR method, is said to be a perfect way to edit genes. Data from publicly available data in the Sequence Read Archive (SRA), which is available through the National Center for Biotechnology Information (NCBI), were randomly screened by interested parties for antlerless farm animal DNA data. Information was recorded in the data bank about the DNA sequences of the Polled (P) gene, which leads to "polledness" or the absence of horns.

CRISPR enthusiasts have been eager to convey that, unlike old-fashioned GMO methods, these newer editing methods should be risk-free. Regardless of where it is used, there should be no risk of unwanted, foreign genes occurring – e.g. Antibiotic-resistant genes, or other unpredictable genes originating from microbes. But antibiotic-resistant genes had been inserted into calves by gene editing, and this has dangerous implications.

What was discovered by chance was that a company had implemented significantly more than a small change. They had also inserted the genes AmpR and NeoR/KanR. These are antibiotic genes that confer resistance to Ampicillin, Neomycin and Kanamycin. These were originally used by the company to develop pure bacterial cultures containing the Polled Celtic allele gene (Pc) for the hereditary absence of horns.

If the sequence for the absence of horns is first linked to these antibiotic-resistant genes, then it will be possible to grow pure bacterial lines with the sequence to prevent horn growth in animals. In a laboratory glass with some antibiotics to kill other bacteria, only those that are genetically modified will succeed in growing.

Technologically introduced antibiotic resistance in cattle can pose a real risk to human health, animal health and the environment. Cattle with an inserted functioning gene for antibiotic resistance will probably be able to tolerate higher concentrations of antibiotics in the diet. This can therefore also lead to a higher use of antibiotics. Intensively farmed farm animals are given antibiotics three times a day to fight bacterial diseases.

It is currently documented approx. 50% increase in the last 10 years with antibiotic-resistant microbes such as Escherichia coli, Salmonella, Campylobacter, and Staphylococci in cattle, chicken and pigs, in Africa, Asia and America. There is a global increase in the number of cases of E. coli and Salmonella with antibiotic resistance (quinolone, gentamycin, colistin). There is up to a 60% increase in Campylobacter antibiotic resistance (tetracycline, quinolones). For Staphylococcus aureus, the resistance rate to all antibiotics (penicillin, erythromycin, tetracycline and oxacillin) in farm animals has become the highest in Asia.

There is a real possibility that antibiotic-resistant genes from bacteria in farm animals will be transferred through plasmid (circular piece of DNA in bacteria, which can contain genes for antibiotic resistance) to bacteria in humans and cause these bacteria to also become antibiotic-resistant. There are cases in China of colistin resistance in both animal and human samples suggesting that resistance in bacteria to colistin in animals has spread to humans.

Knowledge of gene editing
Alarm as antimicrobial resistance surges among chickens, pigs and cattle

PDF articles:
Norris AL, Lee SS, Greenlees KJ, Tadesse DA, Miller FM, 2019. Template plasmid integration in germline genome-edited cattle

Global trends in antimicrobial resistance in animals in low- and middle-income countries.

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