Rodenticide-resistant mutant rats

Rodents are one of the animal pests with the greatest impact on agricultural production and public health, especially the sewer rat (Rattus norvegicus) and the black rat (Rattus rattus). The use of anticoagulant rodenticides is the only effective control method available on a mass scale.

Anticoagulant rodenticides inhibit the enzyme vitamin K 2,3-epoxide reductase (VKORC1) which is responsible for maintaining the balance between its oxidized and reduced forms. The inhibition of VKORC1 prevents the activation of coagulation factors, causing the death of the animal due to internal bleeding. However, heavy use of anticoagulant rodenticides can cause rodents to lose their susceptibility and become resistant to them. Genetic resistance to this type of rodenticide is mainly associated with mutations or single nucleotide polymorphisms in the gene that codes for VKORC1. Any increase in resistance in rodent populations would lead to pest control problems that could cause serious agricultural, livestock, and public health problems.

Azucena Bermejo Nogales, Jose Antonio Rodríguez Martín, Julio Coll and Jose María Navas, researchers at the National Institute for Agricultural and Food Research and Technology (INIA), dependent on the Higher Council for Scientific Research (CSIC) in Spain, with the support of the Association Nacional de Empresas de Sanidad Ambiental (ANECPLA) and various municipalities have studied the mutations associated with resistance to anticoagulant rodenticides. “We have monitored and discovered mutations in rodents that could favor genetic resistance, which provides new data to the scant information that exists in Spain on the increase in resistance to this type of rodenticide,” says Azucena Bermejo.

“The study demonstrates the existence of new mutations in the gene that codes for the enzyme vitamin K 2,3-epoxide reductase (VKORC1) in populations of black and sewer rats in Spain. Through computational analysis we have obtained a first estimate of the possible correlations of the detected mutations with resistance to anticoagulant rodenticides”, adds Dr. Bermejo.

Specimen of sewer rat. (Photo: CDC)

In populations of sewer rats, the S149I mutation was found with frequencies that oscillate depending on the number of samples received. For example, in Madrid the frequency of mutation reaches 21% in the sewerage. The same occurs with the black rat populations, which showed up to four mutations, with a frequency reaching 32% at position S149T, with higher statistical significance than in the case of the sewer rat.

Regarding the computational studies carried out in order to investigate whether the mutations found in the VKORC1 protein could change the affinity of anticoagulant rodenticides, the comparisons between species showed that the black rat needs higher concentrations of this type of rodenticide than the sewer rat. .

The authors of the study conclude that strategies based on integrated pest management should reduce the use of pesticides and restrict them to professional use in order to reduce their possible adverse effects on wildlife and the probability of the appearance of resistance. “For proper management of the use of anticoagulant rodenticides, it is important to identify the evolution of resistance over time, monitoring, among other things, the genetic changes in the gene that codes for VKORC1 in rodent populations” concludes Azucena Bermejo- Walnuts.

The study is entitled “VKORC1 single nucleotide polymorphisms in rodents in Spain”. And it has been published in the academic journal Chemosphere. (Source: INIA / CSIC)