Genome sequences of copper resistant and sensitive Enterococcus faecalis strains isolated from copper-fed pigs in Denmark Original paper

What was studied?

This study investigated the genome sequences of six Enterococcus faecalis strains that were isolated from copper-fed pigs in Denmark. The strains were selected based on their copper resistance or sensitivity, providing insight into the molecular mechanisms underlying copper resistance in E. faecalis. Enterococcus faecalis, a Gram-positive bacterium commonly found in the gastrointestinal tracts of both humans and animals, has been known for its role as a pathogen. The study also examined how copper resistance genes in these strains could potentially co-exist with antibiotic resistance genes, providing valuable insights into the growing concern of multi-drug-resistant pathogens. Comparative genomic analysis was used to assess the differences between copper-resistant and copper-sensitive strains and to identify potential co-transfer of resistance determinants.

Who was studied?

The study involved six E. faecalis strains (S1, S12, S17, S18, S19, and S32), which were isolated from healthy pigs that were fed copper-supplemented diets. These strains were compared in terms of their copper resistance capabilities and their genomic features. Three of the strains (S1, S18, and S32) were identified as copper-resistant, while the other three (S12, S17, and S19) were copper-sensitive. The researchers used whole-genome sequencing and comparative genome analysis to study the genetic makeup of these strains, with a particular focus on genes related to copper and antibiotic resistance.

Most important findings

The genomic analysis revealed significant differences between copper-resistant and copper-sensitive E. faecalis strains. Notably, the copper-resistant strains (S1, S18, and S32) contained genes encoding copper resistance, including the copYABZ operon, which was absent in the copper-sensitive strains. The copA, copB, and copZ genes involved in copper efflux and homeostasis were present in all the strains but were more prominent in the copper-resistant strains. Additionally, a tcrYAZB operon, responsible for high-level copper resistance, was found in the copper-resistant strains, as well as a cueO gene encoding a multicopper oxidase that helps detoxify copper by converting Cu(I) to Cu(II).

The study also identified that the copper-resistant strains contained additional genes related to antibiotic resistance, such as tetM (tetracycline resistance) and vanA (vancomycin resistance). The presence of these genes in the same strains suggests a potential co-transfer mechanism between copper and antibiotic resistance. Furthermore, mobile genetic elements, such as transposases, were found near the copper resistance genes, indicating that copper resistance could be transferred to other bacteria in the environment.

Key implications

The findings highlight the complex relationship between copper resistance and antibiotic resistance in E. faecalis, suggesting that copper supplementation in livestock feed could inadvertently contribute to the development of multidrug-resistant strains. The identification of genetic elements responsible for copper resistance and their co-location with antibiotic resistance genes raises concerns about the spread of resistance through horizontal gene transfer, especially in environments where both copper and antibiotics are used, such as in agriculture.

This study emphasizes the need for careful management of copper use in animal feed, as it may not only contribute to copper resistance in bacteria but also to the emergence of multidrug-resistant pathogens. The genomic insights into E. faecalis resistance mechanisms offer a better understanding of how resistance determinants are transferred and could inform strategies to reduce the spread of resistance in both agricultural and clinical settings. Further research into the environmental impact of copper use in agriculture, and the role of E. faecalis as a reservoir for resistance genes, could help mitigate the risks associated with copper supplementation in livestock.