Evidence of Increasing Antibiotic Resistance Gene Abundances in Archived Soils since 1940
Abstract
Mass production and use of antibiotics and antimicrobials in medicine and agriculture have existed for over 60 years, and has substantially benefited public health and agricultural productivity throughout the world. However, there is growing evidence that resistance to antibiotics (AR) is increasing both in benign and pathogenic bacteria, posing an emerging threat to public and environmental health in the future. Although evidence has existed for years from clinical data of increasing AR, almost no quantitative environmental data exist that span increased industrial antibiotic production in the 1950s to the present; i.e., data that might delineate trends in AR potentially valuable for epidemiological studies. To address this critical knowledge gap, we speculated that AR levels might be apparent in historic soil archives as evidenced by antibiotic resistance gene (ARG) abundances over time. Accordingly, DNA was extracted from five long-term soil-series from different locations in The Netherlands that spanned 1940 to 2008, and 16S rRNA gene and 18 ARG abundances from different major antibiotic classes were quantified. Results show that ARG from all classes of antibiotics tested have significantly increased since 1940, but especially within the tetracyclines, with some individual ARG being >15 times more abundant now than in the 1970s. This is noteworthy because waste management procedures have broadly improved and stricter rules on nontherapeutic antibiotic use in agriculture are being promulgated. Although these data are local to The Netherlands, they suggest basal environmental levels of ARG still might be increasing, which has implications to similar locations around the world
Although this study shows trends of increasing resistance in The Netherlands, the results argue for more and similar studies around the world because of the work’s implications. For example, our results imply there may be a progressively increasing chance of encountering organisms in nature that are resistant to antimicrobial therapy. With horizontal exchange of genetic material and increased diversity of bacterial hosts, each potential extrinsic source of resistance genes, either in the environment or among commensal organisms, increases the chance of acquired resistance in a pathogen (38). Further, given that soils might act as harbors of beneficial determinants to resident organisms, past antibiotic and antimicrobial exposure may have a lingering effect on the resistance gene pool, even when more prudent antibacterial use is common, although this must still be proven. Overall, our data imply that environmental factors promoting AR proliferation may not have yet been fully defined, which argues for further directed research into links between AR, and environmental and anthropogenic causes. The Standing Medical Advisory Committee’s report, The Path of Least Resistance (39), stated “.. .there is an uneasy sense that micro-organisms are ‘getting ahead’ and that therapeutic options are narrowing”, and our results hint that increasing resistance in soil bacteria may be another factor impacting our battle against global AR.
