New polymorphisms of Vkork1 gene related to anticoagulant resistance of rats and mice in Italy.

Background: Anticoagulant rodenticides (ARs) are a very effective tool to control rodent pest populations. Nevertheless, AR resistance has been documented worldwide. ARs block the cycle of vitamin K, leading to the death of the animal by internal bleeding: mutations in Vkorc1 gene can cause resistance. The spreading of AR-resistant rodents could lead to an increase of their populations, the associated diffusion of zoonotic pathogens, and to the amplified exposure of non-target animals to ARs, thus it is important to study its diffusion widely. This study aimed to report firstly the presence of Vkorc1 mutations in synanthropic rodents from the Emilia-Romagna region, Italy, and evaluate their role in resistance by means of molecular docking analysis.

Results: A total of 67 animals were analyzed: 24 Rattus norvegicus, 35 Rattus rattus and eight Mus musculus. Single nucleotide polymorphisms (SNPs) associated with AR resistance, in homozygosis or heterozygosis, were detected in 6/8 mice, on codons 128 and 139, and 13/24 R. norvegicus, on codons 61 and 139, and in 10/35 R. rattus, on codon 59. Furthermore, several newly described missense mutations were detected in all the tested species: the molecular docking analysis suggests a role of some of these (e.g., I123S and F87L) in resistance to brodifacoum, both in rats and in mice.

Conclusion: The discovery of AR resistance SNPs in the 43.28% of tested rodents sounds as an alarm bell that requires the introduction of an integrated control approach, where ARs are not used routinely, but under specific monitoring evaluation. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.