HME-AMR: Investigating the role of heavy metals in the environment as a selective pressure for the dissemination of antimicrobial resistance
A key element in managing antimicrobial resistance (AMR) in the One Health paradigm is to reduce the dissemination of resistance genes between microorganisms in the agri-food environment. A crucial mechanism for such dissemination is via horizontal gene transfer (HGT) of AMR encoding mobile genetic elements. This is particularly the case for Enterobacteriaceae where a multi-drug resistant (MDR) phenotype is increasingly being observed. This mobility shapes the resistome; the collection of all genes that directly or indirectly contributes to antibiotic resistance in a particular niche. It is recognised that a reservoir of AMR genes in the environment provides the possibility for transfer of these genes to human pathogenic bacteria via zoonotic pathways.
Selective pressures drive bacterial populations to evolve and may promote the dissemination of AMR genes, in the human and animal gut, or in the environment. However, there is limited information about the impact of selective pressures in the agri-food environment on HGT between microorganisms. One of the factors which can act as a selective pressure and can influence this HGT is the presence of heavy metals. Resistance to these metals may lead to the co-selection of antibiotic resistance genes, as antibiotic resistance genes can be located on the same genetic element as metal resistance genes. Cross resistance is also a possibility, where a heavy metal resistance mechanism such as non-specific membrane transporter may also facilitate antibiotic resistance.
Heavy metals occur ubiquitously in the agri-food environment and sometimes in high concentrations in soil. In food animal production, heavy metals such as zinc and copper are frequently added to animal feed to promote growth and health. Such heavy metals added to animal feed may not be fully absorbed from the animal gut and are excreted in faeces into the environment. One study demonstrated that 90% of the in-feed copper and zinc was shed in faeces and thus landspreading of manure may widely disseminate such heavy metals and also create a driver for AMR development and spread.
Recent studies have demonstrated that MDR Salmonella Typhimurium obtained from foods and food animals frequently displayed resistance to zinc (78%) and copper (68%), with the presence of corresponding heavy metal resistance genes. A similar study of Salmonella in China also demonstrated the co-presence of antibiotic and heavy metal resistance genes in retail foods and a US study demonstrated co-presence in dairy barn samples. Xue and colleagues (2015) also demonstrated correlations between heavy metal and antibiotic resistance genes in Staphylococcus aureus obtained from milk. However, there are very few studies available looking at the resistome in the environment and its influencers in a broader context, which may have significant impact on the dissemination of AMR.
It is recognised that a One Health approach is required to tackle antimicrobial resistance. This includes the role the environment, and the food production environment in particular, plays. Very limited information is available regarding the impact of selective pressures such as heavy metals which may be present in the environment on the mobilisation of antimicrobial resistance and its potential transfer into the food chain. There is a clear need for more data on the impact of heavy metal concentrations in food production settings and their potential impact on the co-selection and dissemination of AMR in the environment and the food chain, and this is therefore the driver for this project.