The Link between Antimicrobial Resistance and the Content of Potentially Toxic Metals in Soil and Fertilising Products
Authors: Wastson Yngvild , Skjerve Eystein , Yazdankhah Siamak , Eckner Karl , Kapperud Georg , Lassen Jørgen Fredrik , Narvhus Judith , Nesbakken Truls , Robertson Lucy , Rosnes Jan Thomas , Skjerdal Olaug Taran , Vold Line 
Published: July 2019

Potentially toxic metals (PTM), along with PTM-resistant bacteria and PTM-resistance genes may be introduced to soil and water through sewage systems, direct excretion, land application of biosolids (organic matter recycled from sewage, especially for use in agriculture) or animal manures as fertilisers, and irrigation with wastewater or treated effluents.
The Norwegian Food Safety Authority (NFSA) asked the Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) for an assessment of the link between antimicrobial resistance (AMR) and potentially toxic metals (PTM) in soil and fertilising products.
The NFSA would like VKM to give an opinion on the following question related to the influence of potentially toxic metals on antimicrobial resistance:

Can the content of arsenic (As), cadmium (Cd), chromium (CrIII + CrVI), copper (Cu), lead (Pb), mercury (Hg), nickel (Ni), and zinc (Zn) in soil and fertilising products that are relevant for Norway play a role in the development, spreading, and persistence of bacterial resistance to these elements, as well as cross or co-resistance to antimicrobial agents?

VKM appointed a working group, consisting of two members of the Panel on Biological Hazards, to prepare a draft Opinion document and answer the questions. The Panel on Biological Hazards has reviewed and revised the draft prepared by the working group and approved the Opinion document “The link between antimicrobial resistance and the content of potentially toxic metals in soil and fertilising products”.
In this report we assess the following PTM: arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni), mercury (Hg), lead (Pb), and zinc (Zn), because of their possible presence in fertilisers and their potential to induce AMR in bacteria.
This assessment is based on internationally published data. There is no systematic monitoring for toxic metals in soils in Norway, and the levels are expected to be highly variable depending on the input sources, previous and current agricultural practices, and the characteristics of the soil. Data on PTM in fertilising products added to soil are also fragmented and limited. Fertilising materials, in the form of sewage sludge or livestock manure, will add toxic metals to the existing levels in soil, and in areas of intensive agriculture, the levels will be expected to be highest. The additive effect of toxic metals in fertilising materials must be assessed from a long-term perspective, as these metals accumulate in the environment.
Development of AMR can be partly regarded as a dose- and time-dependant response to exposure to different drivers for resistance. There is an indication that the presence of potentially toxic metals is a driver for development of AMR in exposed bacteria, but the dose and time exposure most likely to cause this effect is not known. Investigation of PTM-driven co-selection of AMR in environments impacted by agriculture and aquaculture should focus especially on Cu and Zn, which are added to animal feed, and on Cd because of its high concentration, in comparison with other PTM, in inorganic fertilising products. The naturally occurring background resistance in environmental bacteria complicates the estimation of the effect of PTM exposure on development of resistance. In addition, it is difficult to distinguish between the natural resistome and an elevated abundance of AMR in environmental samples.
Spreading of resistance towards the PTM evaluated in this assessment involves cross- and co-resistance to antimicrobial agents used in prophylaxis and therapy in animals and people. Most important are those cases where toxic metal resistance is coupled to resistance towards highly important and critically important antibiotics. This has been described in some of the published articles included in this assessment. We do not fully understand the mechanisms behind persistence of AMR, and removing drivers for development and spread of resistance may result in a decrease in the levels of resistance, but not necessarily full disappearance.
There is lack of knowledge regarding links between the level and concentration of PTM in fertilising products and soil and development of resistance in bacteria. Data regarding the routes and frequencies of transmission of AMR from bacteria of environmental origin to bacteria of animal and human origin were lacking in the published articles reviewed here. Due to the lack of such data, it is difficult to estimate the probability of development, transmission, and persistence of PTM resistance in the Norwegian environment. More research is needed to explain the relationship between development of resistance against potential toxic metals and resistance toward antimicrobial agents in bacteria.