Abstract
Antimicrobial resistance is a growing public health challenge worldwide, with agricultural use of antimicrobials being one major contributor to the emergence and dissemination of antimicrobial resistance (AMR). Globally, most antimicrobials are used in industrial food animal production, a major context for microbiomes encountering low-doses or subtherapeutic-levels of antimicrobial agents from all mechanistic classes. This modern practice exerts broad eco-evolutionary effects on the gut microbiome of food animals, which is subsequently transferred to animal waste. This waste contains complex constituents that are challenging to treat, including AMR determinants and low-dose antimicrobials. Unconfined storage or land deposition of a large volume of animal waste causes its wide contact with the environment and drives the expansion of the environmental resistome through mobilome facilitated horizontal genet transfer. The expanded environmental resistome, which encompasses both natural constituents and anthropogenic inputs, can persist under multiple stressors from agriculture and may re-enter humans, thus posing a public health risk to humans. For these reasons, this review focuses on agricultural antimicrobial use as a laboratory for understanding low-dose antimicrobials as drivers of resistome expansion, briefly summarizes current knowledge on this topic, highlights the importance of research specifically on environmental microbial ecosystems considering AMR as environmental pollution, and calls attention to the needs for longitudinal studies at the systems level.
Highlights
The intensive production of food animals is a major context for microbiomes encountering low-doses or subtherapeutic-levels of diverse classes of antimicrobial agents
This review focuses on food animal production as an important laboratory for understanding the eco- evolutionary mechanisms involved in bacterial responses to low-dose, sub-therapeutic pressures associated with antimicrobials
Cavaco et al (2011) reported that cadmium and zinc drive co-selection for methicillin resistance in Staphylococcus aureus through horizontal transfer of plasmids containing genes for both methicillin and metal resistance. These findings indicate the need to consider interaction effects of antimicrobials and other stressors within agricultural settings in terms of driving antimicrobial resistance (AMR) emergence and dissemination, www.frontiersin.org in light of the complex nature of manufactured feeds utilized in food animal production
Summary
The intensive production of food animals is a major context for microbiomes encountering low-doses or subtherapeutic-levels of diverse classes of antimicrobial agents. A majority of agricultural antimicrobials are used as feed additives for growth promotion in livestock and poultry (Silbergeld et al, 2008). This use began in the 1940s in the US, soon after the initiation of large-scale production of these drugs for clinical medicine. From early in the history of GPA use, it was recognized that the gut microbiome of poultry was responding to selection for resistance to drugs in feeds. Jukes acknowledged this as a truism, www.frontiersin.org
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