Antibiotic resistance in the environment

Abstract

Antibiotic resistance is a global health challenge, involving the transfer of bacteria and genes between humans, animals and the environment. Although multiple barriers restrict the flow of both bacteria and genes, pathogens recurrently acquire new resistance factors from other species, thereby reducing our ability to prevent and treat bacterial infections. Evolutionary events that lead to the emergence of new resistance factors in pathogens are rare and challenging to predict, but may be associated with vast ramifications. Transmission events of already widespread resistant strains are, on the other hand, common, quantifiable and more predictable, but the consequences of each event are limited. Quantifying the pathways and identifying the drivers of and bottlenecks for environmental evolution and transmission of antibiotic resistance are key components to understand and manage the resistance crisis as a whole. In this Review, we present our current understanding of the roles of the environment, including antibiotic pollution, in resistance evolution, in transmission and as a mere reflection of the regional antibiotic resistance situation in the clinic. We provide a perspective on current evidence, describe risk scenarios, discuss methods for surveillance and the assessment of potential drivers, and finally identify some actions to mitigate risks.

Fig. 1. The role of the environment in the emergence of new resistance genes in pathogens.

Conceptual illustration of how evolution leading to the emergence of a new antibiotic resistance gene (ARG; red) in pathogens can involve the environment and/or the human/domestic animal microbiota to different extents. The evolution typically occurs in steps, as indicated by the grey arrows. The first can be the association of a chromosomal ARG (red) with, for example, insertions sequences (ISs; green), which provide intracellular mobility. Intracellular relocation to, for example, a plasmid allows the ARG to move horizontally across strains and species. The mobilized ARG can then be transferred to a pathogen in one or several steps. In the most extreme cases, all genetic steps occur in either the environment (top) or in the human or domestic animal microbiota (bottom). However, at any stage bacteria carrying the ARG may move physically from the environment to the human or domestic animal microbiota, as illustrated by the differently coloured, thick arrows. The genetic reservoir is considerably larger in the environment, suggesting that the source for new ARGs is often environmental bacteria. By contrast, reoccurring, strong antibiotic selection pressures and close contact with pathogens are more common in humans and domestic animals, although some external environments also share those drivers. Environmental release of faecal bacteria may also boost the evolutionary process by providing genetic elements that are adapted to capture and transfer ARGs. How common the different depicted scenarios are is still largely unknown. A better understanding of how often the different evolutionary steps occur in the environment versus the human or domestic animal microbiota and what drivers are most important would enable more efficient resource allocation to limit or delay the emergence of new ARGs in pathogens.

Fig. 2. Antibiotic concentrations in selected aquatic environments.

Different types of sources of antibiotic pollution typically give rise to different levels of exposure to aquatic bacterial communities. This, in turn, provides a reflection of the probability of environmental selection. Although very much a simplification, the ranges of typical antibiotic concentrations in aquatic environments exposed to excreted antibiotics from human use are depicted for the sea, rivers, treated and untreated municipal sewage effluents and untreated hospital effluents. Sea and river environments refer to those contaminated with treated municipal sewage. In addition, surface waters polluted directly by wastewater from drug manufacturing are included. As a comparison, typical minimal inhibitory concentrations (MICs) for many antibiotic–pathogen combinations often fall within the 10–10,000 µg l⁻¹ range. As both depicted environmental concentrations and typical MICs are simplified illustrations representing many different antibiotics, an overlap between the two is not necessarily evidence of selection, unless there is overlap also for individual antibiotics. Note also that selection may occur at concentrations below the MIC.

Fig. 3. Pathways for transmission of bacterial pathogens and recruitment of resistance genes from the environmental microbiota.

The dominating routes for transmission of (resistant) pathogens (solid arrows) are between humans, between domestic animals and sometimes between animals and humans. These transmission routes can be direct or indirect via the external environment (lower part of the figure), often through faecal contamination. The consequences of each transmission event are limited, and the risks are in principle quantifiable. There are also rarer and less predictable evolutionary events where new resistance factors are recruited to pathogens by horizontal gene transfer from the diverse, environmental microbiota (dashed arrows). Such transfer events may occur either in the environment or within the human or domestic animal microbiota. The consequences of single gene transfer events may be vast and are irreversible.