Antibiotic resistance

The lab has a long history of studying the role of the environment in antibiotic resistance development. Most of this work consists of analysis of DNA sequence data from entire microbial communities – so called metagenomics – to detect resistance genes, mobile genetic elements, taxonomic compositions and genes responsible for other biological functions in these communities. An important aspect of this work is the development of software tools and workflows for these tasks. We have worked with a variety of sample types, including human feces, lake sediments, microcosm biofilms, sewage and sludge. A central outcome of our previous research is the realization that environmental antibiotic selection pressures play a central role in the process of resistance development, as they provide a window of growth advantage for bacteria carrying antibiotic resistance genes otherwise associated with high fitness costs. In accordance, we have further explored of the concentrations of antibiotics (and other co-selective substances) required to provide resistant bacteria with a fitness advantage. A second important recognition of our previous work is that the barriers to dissemination of resistant bacteria are very poorly understood, and that a better ecological understanding of human-associated bacteria, their dispersal and environmental interactions is fundamental to curb the resistance problem.

One aim of our research is to provide quantitative data to populate risk models for resistance emergence and propagation. Specifically, we focus on concentrations of antibiotics that can drive selection for resistant bacteria and transfer of resistance genes. Another type of quantitative data that is currently lacking is information on the typical background levels of resistant bacteria and resistance genes in different environments, particularly those where humans interact with resistant bacteria from the environment. The lab coordinates EMBARK which will generate such background data from relatively pristine and human-impacted environments, as well as from the human microbiome. This will provide a baseline for future monitoring efforts for antibiotic resistance. The project also involves standardizing protocols and making different monitoring practices comparative, which will enable a much broader use of the monitoring data that is already being generated.

Open questions of interest

  • Which environments constitute particular high-risk settings for resistance development?
  • How does the environment contribute to the emergence of novel resistance determinants?
  • Which are the important dispersal routes for antibiotic resistance genes and resistant microbes to the human microbiome?
  • What are the minimal selective concentrations of antibiotics (and other chemicals) in complex communities?
  • What are the secondary (indirect) effects of antibiotic exposure and increasing antibiotic resistance in microbial communities?
  • How can we make monitoring of antibiotic resistance in the environment cost-efficient?

Key publications

  • Bengtsson-Palme J, Kristiansson E, Larsson DGJ: Environmental factors influencing the development and spread of antibiotic resistance. FEMS Microbiology Reviews, 42, 1, 68–80 (2018). doi: 10.1093/femsre/fux053 [Paper link] (Editor’s choice)
  • Bahram M°, Hildebrand F°, Forslund SK, Anderson JL, Soudzilovskaia NA, Bodegom PM, Bengtsson-Palme J, Anslan S, Coelho LP, Harend H, Huerta-Cepas J, Medema MH, Maltz MR, Mundra S, Olsson PA, Pent M, Põlme S, Sunagawa S, Ryberg M, Tedersoo L, Bork P: Structure and function of the global topsoil microbiome. Nature, 560, 7717, 233–237 (2018). doi: 10.1038/s41586-018-0386-6 [Paper link]
  • Bengtsson-Palme J: The diversity of uncharacterized antibiotic resistance genes can be predicted from known gene variants – but not always. Microbiome, 6, 125 (2018). doi: 10.1186/s40168-018-0508-2 [Paper link]
  • Bengtsson-Palme J, Jonsson V, Heß S: What is the role of the environment in the emergence of novel antibiotic resistance genes? A modelling approach. Environmental Science & Technology, 55, 23, 15734–15743 (2021). doi: 10.1021/acs.est.1c02977 [Paper link]
  • Bengtsson-Palme J, Larsson DGJ: Antibiotic resistance genes in the environment: prioritizing risks. Nature Reviews Microbiology, 13, 369 (2015). doi: 10.1038/nrmicro3399-c1 [Paper link]
  • Bengtsson-Palme J, Boulund F, Fick J, Kristiansson E, Larsson DGJ: Shotgun metagenomics reveals a wide array of antibiotic resistance genes and mobile elements in a polluted lake in India. Frontiers in Microbiology, 5, 648 (2014). doi: 10.3389/fmicb.2014.00648 [Paper link]
  • Bengtsson-Palme J, Angelin M, Huss M, Kjellqvist S, Kristiansson E, Palmgren H, Larsson DGJ, Johansson A: The human gut microbiome as a transporter of antibiotic resistance genes between continents. Antimicrobial Agents and Chemotherapy, 59, 10, 6551-6560 (2015). doi: 10.1128/AAC.00933-15 [Paper link]
  • Bengtsson-Palme J, Hammarén R, Pal C, Östman M, Björlenius B, Flach C-F, Kristiansson E, Fick J, Tysklind M, Larsson DGJ: Elucidating selection processes for antibiotic resistance in sewage treatment plants using metagenomics. Science of the Total Environment, 572, 697–712 (2016). doi: 10.1016/j.scitotenv.2016.06.228 [Paper link]
  • Bengtsson-Palme J, Larsson DGJ: Concentrations of antibiotics predicted to select for resistant bacteria: Proposed limits for environmental regulation. Environment International, 86, 140-149 (2016). doi: 10.1016/j.envint.2015.10.015 [Paper link]
  • Pal C, Bengtsson-Palme J, Kristiansson E, Larsson DGJ: The structure and diversity of human, animal and environmental resistomes. Microbiome, 4, 54 (2016). doi: 10.1186/s40168-016-0199-5 [Paper link]

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