Environmental factors influencing the development and spread of antibiotic resistance

Abstract

Antibiotic resistance and its wider implications present us with a growing healthcare crisis. Recent research points to the environment as an important component for the transmission of resistant bacteria and in the emergence of resistant pathogens. However, a deeper understanding of the evolutionary and ecological processes that lead to clinical appearance of resistance genes is still lacking, as is knowledge of environmental dispersal barriers. This calls for better models of how resistance genes evolve, are mobilized, transferred and disseminated in the environment. Here, we attempt to define the ecological and evolutionary environmental factors that contribute to resistance development and transmission. Although mobilization of resistance genes likely occurs continuously, the great majority of such genetic events do not lead to the establishment of novel resistance factors in bacterial populations, unless there is a selection pressure for maintaining them or their fitness costs are negligible. To enable preventative measures it is therefore critical to investigate under what conditions and to what extent environmental selection for resistance takes place. In addition, understanding dispersal barriers is not only key to evaluate risks, but also to prevent resistant pathogens, as well as novel resistance genes, from reaching humans.

Keywords: antimicrobial resistance; dissemination; fitness costs; horizontal gene transfer; human health risks; microbial ecology.

Figure 1.

An overview of the main roles of the external environment in antibiotic resistance development and dissemination. Note that none of these processes requires a selection pressure for resistance to operate, although such a selection pressure would facilitate both maintenance and recruitment of resistance genes. Antibiotic exposure may select for resistant bacteria during dispersal if those bacteria are able to grow also in the external environment, which is the case for many opportunistic pathogens. Furthermore, the environment also serves as a source of opportunistic pathogens that are already resistant, or may acquire resistance genes from other human-associated bacteria in or on the human body and then cause resistant infections at a later stage. While both known and novel resistance genes may be recruited from the environmental resistome, the most severe long-term health consequences of such acquisitions are likely when genes not currently present in pathogens are added to their resistance repertoire.

Figure 2.

The role of the environment in the recruitment of antibiotic resistance genes (ARGs) to human pathogens includes four major steps: (1) emergence of novel resistance factors in the environment, (2) mobilization onto mobile genetic elements, (3) transfer of ARGs to human pathogens, and (4) dissemination of ARGs into the human microbiome. The width of each arrow roughly corresponds to the assumed frequency of each event, although this is of course largely speculative. Many events are likely more frequent when antibiotic selection pressure is stronger or recurrent. Still, due to the much larger numbers of environmental bacteria than human- and animal-associated, environmental emergence and mobilization of ARGs is probably common on a global scale. Note that the focus of this figure is on the processes involving the external environment.