Co-selection for antibiotic resistance by environmental contaminants

Abstract

The environment is increasingly recognised as a hotspot for the selection and dissemination of antibiotic resistant bacteria and antibiotic resistance genes. These can be selected for by antibiotics and non-antibiotic agents (such as metals and biocides), with the evidence to support this well established by observational and experimental studies. However, there is emerging evidence to suggest that plant protection products (such as herbicides), and non-antibiotic drugs (such as chemotherapeutic agents), can also co-select for antibiotic resistance. This review aims to provide an overview of four classes of non-antibiotic agents (metals, biocides, plant protection products, and non-antibiotic drugs) and how they may co-select for antibiotic resistance, with a particular focus on the environment. It also aims to identify key knowledge gaps that should be addressed in future work, to better understand these potential co-selective agents.

Fig. 1. Co-selection mechanisms of cross-resistance, co-resistance and co-regulation.

Cross-resistance occurs when a mechanism provides resistance to two or more agents (e.g., a multi-drug efflux pump). In this figure, the AcrAB-TolC efflux pump gene is shown, which can pump out of the cell multiple antibiotics and biocides, non-antibiotic drugs^,, and plant protection products^,. Co-resistance occurs when two genes are physically linked on a piece of DNA so are inherited together e.g., an antibiotic and metal resistance gene located on a plasmid. In this figure, the metal resistance gene arsB and the antibiotic resistance gene blaTEM-1 are both present on a plasmid and can be inherited together. Co-regulation occurs when the translational or transcriptional responses to one agent leads to a co-ordinated response to more than one agent (e.g., an antibiotic or biocide could lead to expression of a multi-drug efflux pump). In this figure, the transcriptional pathways of the mex operon and the czc operon are linked so that expression of either leads to the expression of both the czc and oprD efflux pumps. Created with Biorender.