Learning from agriculture: understanding low-dose antimicrobials as drivers of resistome expansion

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.

Keywords: agriculture; antimicrobials; environmental pollution; metals; microbiome; mobilome; resistome.

Figure 1

(A) (left) Pigs in confinement house (photo USDA). Note slatted floor; wastes (including excreta and spilled feed) accumulate on this surface and are periodically washed down into a cesspit below the building. (right) A view of a swine production operation showing open cesspits that collect drainage from animal houses; disposal of these wastes involves spraying of liquids (photo S Wing). (B) (left) Chickens in a Maryland poultry house. Flocks are housed directly on litter, which contains excreta (as evident from the birds) as well as spilled feed. Litter is removed infrequently from poultry houses (photo J Graham). (right) The lower Pocomoke River, with poultry houses and land disposal of poultry waste (source: Integration and Application Network, University of Maryland Center for Environmental Sciences).

Figure 2

Conceptual framework for understanding flow of resistance genes and mobile genetic elements across microbiomes within food animals, the environment, and human populations (based on Davis et al., 2011).