EFSA evaluates antibiotic resistance marker genes in GM plants

An EFSA statement[1] has been published today that provides a consolidated overview of the use of antibiotic resistance marker genes (ARMG)[2] in GM plants, including a joint scientific opinion of the GMO and BIOHAZ Panels. The Panels concluded that, according to information currently available, adverse effects on human health and the environment resulting from the transfer of the two antibiotic resistance marker genes, nptII and aadA, from GM plants to bacteria, associated with use of GM plants, are unlikely. Uncertainties in this opinion are due to limitations related, among others, to sampling and detection, as well as challenges in estimating exposure levels and the inability to assign transferable resistance genes to a defined source. Two members of the BIOHAZ Panel expressed minority opinions concerning the possibility of adverse effects of antibiotic resistance marker genes on human health and the environment.

In another opinion, the GMO Panel reviewed its previous assessments of individual GM plants containing ARMG taking into account the findings and conclusions of the joint opinion of the GMO and BIOHAZ Panels. The GMO Panel concluded that its previous risk assessments on the use of the nptII marker gene in GM plants are consistent with the risk assessment strategy described in the joint opinion and that no new scientific evidence has become available that would prompt it to change its previous opinions[3] on these GM plants.

Following the adoption of the joint opinion of the GMO and BIOHAZ Panels, EFSA asked the panels to consider whether the minority opinions required any clarification of the joint opinion or additional scientific work. The Panel chairs responded that the minority opinions had been extensively considered during the preparation of the joint opinion and no further clarification or scientific work were needed at this time.

In their joint opinion, the GMO and BIOHAZ Panels concluded that transfers of ARMG from GM plants to bacteria have not been shown to occur either in natural conditions or in the laboratory. The key barrier to stable uptake of antibiotic resistance marker genes from GM plants to bacteria is the lack of DNA sequence identity between plants and bacteria.

The Panels concluded that the antibiotic resistance genes nptII and aadA occur at different frequencies in different bacterial species and strains, and environments. Recent analyses of total bacterial populations using the most advanced technologies[4] have demonstrated that resistance genes to the antibiotics kanamycin, neomycin and streptomycin are present in all environments investigated. The presence of antibiotics in the environment and antibiotic usage are key factors in driving the selection and dissemination of antibiotic resistance genes.

The Panels underlined limitations related among others to sampling, detection, challenges in estimating exposure levels and the inability to assign gene transfer to a defined source. Sampling and detection issues are technical aspects of experiments which may limit the validity of results. Furthermore, it is often not possible to find out precisely from which organism an ARM gene present in another organism may have originated nor to give a precise estimation of the extent of the phenomenon[5].

In collaboration with the European Medicines Agency (EMEA) and the European Centre for Disease Prevention and Control (ECDC), the Panels also considered the clinical importance for human and veterinary medicine of the antibiotics to which the ARMG confer resistance. NptII confers resistance to the antibiotics kanamycin and neomycin. These are categorised by the World Health Organization (WHO) as ‘highly important antimicrobials’. Kanamycin is used as a second-line antibiotic for the treatment of infections with multiple drug-resistant tuberculosis (MTB); increasing resistance of MTB to such antibiotics is of concern globally. However, the Panels noted that nptII has not been implicated in resistance to kanamycin in the treatment of MTB.

The GMO Panel also reviewed its previous opinions on the use of nptII in GM plants following the findings from the joint opinion of the GMO and BIOHAZ Panels. The GMO Panel concluded, in another opinion, that its previous risk assessments on the use of nptII in maize MON 863 and hybrids, as well as starch potato EH92-527-1, are in line with the risk assessment strategy described in the joint opinion of the GMO and BIOHAZ Panels. The GMO Panel also underlined that no new scientific evidence has become available that would prompt the Panel to change its previous opinions on these GM plants.

[1] The statement incorporates a joint opinion of the GMO and BIOHAZ Panels, another opinion of the GMO Panel, a letter from EFSA to the Chairs of the Scientific Committee, the GMO and BIOHAZ Panels and a response from the Chairs to that letter.
[2] Marker genes encoding resistance to specific antibiotics may be used in genetic modification to help identify GM cells among the untransformed cells.
[3] Previous opinions include: “EFSA provides scientific advice on the use of antibiotic resistance marker genes in genetically modified plants” of 19 April 2004 ( EFSA provides scientific advice on the use of antibiotic resistance marker genes in genetically modified plants ) and “EFSA GMO Panel reconfirms that the use of the nptII gene as a selectable marker in GM plants does not pose a risk to human or animal health or the environment” of 13 April 2007 ( EFSA GMO Panel reconfirms that the use of the nptII gene as a selectable marker in GM plants does not pose a risk to human or animal health or the environment ).
[4] Such as metagenomics, which allow analysis of entire microbial communities and avoid the need to isolate and culture individual microbial species.
[5] For instance, bacteria with the resistance gene are already naturally present in the environment and could be the source of the ARM gene that is found in other bacteria.

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