Environmental dissemination of antibiotic resistance genes and correlation to anthropogenic contamination with antibiotics

Abstract

Antibiotic resistance is a growing problem which threatens modern healthcare globally. Resistance has traditionally been viewed as a clinical problem, but recently non-clinical environments have been highlighted as an important factor in the dissemination of antibiotic resistance genes (ARGs). Horizontal gene transfer (HGT) events are likely to be common in aquatic environments; integrons in particular are well suited for mediating environmental dissemination of ARGs. A growing body of evidence suggests that ARGs are ubiquitous in natural environments. Particularly, elevated levels of ARGs and integrons in aquatic environments are correlated to proximity to anthropogenic activities. The source of this increase is likely to be routine discharge of antibiotics and resistance genes, for example, via wastewater or run-off from livestock facilities and agriculture. While very high levels of antibiotic contamination are likely to select for resistant bacteria directly, the role of sub-inhibitory concentrations of antibiotics in environmental antibiotic resistance dissemination remains unclear. In vitro studies have shown that low levels of antibiotics can select for resistant mutants and also facilitate HGT, indicating the need for caution. Overall, it is becoming increasingly clear that the environment plays an important role in dissemination of antibiotic resistance; further studies are needed to elucidate key aspects of this process. Importantly, the levels of environmental antibiotic contamination at which resistant bacteria are selected for and HGT is facilitated at should be determined. This would enable better risk analyses and facilitate measures for preventing dissemination and development of antibiotic resistance in the environment.

Keywords: antibiotic resistance; antibiotics; environment; horizontal gene transfer; integrons.

Fig. 1

The basic structure of a class 1 integron. The gene intI1 encodes a site-specific integrase which can excise and integrate gene cassettes at the site-specific integration site attI. In this example, the integron contains three gene cassettes denoted as GC1, GC2, and GC3. Expression of the gene cassettes is induced by the promoter P_C. Class 1 integrons also consist of two conserved genes at the 3′-end, quarternary ammonium compound resistance gene qacEΔ1 and sulphonamide resistance gene sulI.

Fig. 2

Antibiotics and antibiotic resistance genes (ARGs) can enter and re-emerge in humans via the environment by a number of different routes. For example, antibiotics and ARGs from patients taking antibiotics can end up in various environments (e.g. surface water) via excrements which pass through the wastewater treatment system. The commixture of antibiotics, ARGs and resident environmental bacteria at these locations provide an ideal opportunity for ARGs to develop and disseminate in the bacterial community.