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Projects

Summary of ongoing projects


The Environment as a Driver of Antibiotic Resistance - EDAR

Research environment funded by the Swedish Research Council VR (Medicine and Health) (22.4 MSEK) for the period 2019-2024. The research is led by Joakim Larsson in collaboration with Carl-Fredrik Flach and Christian Munthe (University of Gothenburg), Ramanan Laxminarayan (University of Princeton and CDDEP, USA), Erik Kristiansson (Chalmers), and Jerker Fick (Umeå university).

The emergence and global dissemination of antibiotic resistant bacteria pose a serious threat to public health. The environment contributes to these processes in two ways - as a transmission route for certain resistant bacterial pathogens, and as a source for antibiotic resistance genes and resistance plasmids that over time are recruited into human pathogens through horizontal gene transfer. This multidisciplinary project address several critical knowledge gaps related to the environmental dimensions of antibiotic resistance. We aim to: 1. Understand the origin and evolution of antibiotic resistance, i.e. in what species and from what environments they likely were mobilized and transferred 2. Identify already mobilized resistance genes to last-resort antibiotics that have not (yet) been described in pathogens. 3. Understand drivers and mechanisms of resistance evolution (selection, mobilization, transfer) in the environment. 4. Provide an economic analysis of the costs and benefits of environmental interventions. 5. Analyze incentives and counterincentives for such mitigations. Filling these knowledge gaps will significantly improve our scientific understanding of what role the environment plays in the emergence and dissemination of antibiotic resistance. It would also aid in scaling and directing measures to effectively manage resistance threats arising from the environment. In that way, the proposed research will benefit long-term, public health.

 

The role of the environment in the selection and evolution of antibiotic resistance

Project funded by the Swedish Research Council VR (Medicine and Health) (5.6 MSEK) and the Swedish Research Council FORMAS (3 MSEK/year) for the period 2019-2021. The project is led by Joakim Larsson in collaboration with Carl-Fredrik Flach and Rosmarie Friemann (University of Gothenburg), Erik Kristiansson(Chalmers), and Jerker Fick (Umeå university).

The rapidly evolving problem with antibiotic resistant bacteria has emerged as one of the most severe threats to public health globally. It is recognized that environmental bacteria provide a high diversity of antibiotic resistance genes that evolved long before mankind started to use antibiotics as clinical agents. Over the past decades, however, pathogens have acquired more and more resistance determinants through horizontal gene transfer under a selection pressure from antibiotics. This project combines classical bacterial culturing, metagenomic DNA sequencing, bioinformatics analyses, advanced molecular biology, X-ray crystallography and analytical chemistry to address three core knowledge gaps in this evolutionary process. These are: 1) Understanding the relevance of environmental antibiotic pollution from different sources in the selection of resistance 2) Clarifying the evolutionary origin of antibiotic resistance genes, including mechanisms involved, i.e. learning from history about where the risks for transfer are greatest, and 3) Improving our knowledge of the environmental antibiotic resistance reservoir, with particular focus on those that have acquired mobility. The proposed research aim to better understand of the role of the environment in the evolution of antibiotic resistant pathogens, and ultimately also inform management.

 

Centre for Antibiotic Resistance Research at the University of Gothenburg (CARe)

Funding for an interdisciplinary research centre funded by the University of Gothenburg 2016-2022 and hosted by the Institute of Biomedicine. In total ~50 MSEK is budgeted, with 21.4MSEK allocated the first three years. Joakim Larsson directs the center, and in total 30 principal investigators from six faculties and three core external partners are engaged (see figure).

Main research themes of CARe and the different core partners involved. The theme interventions integrate with all other themes. Education & outreach activities cover all themes.

The threat of antibiotic resistant bacteria is a multifaceted challenge with high demands on interdisciplinary research. CARe will take advantage of diverse expertise representing six faculties and a broad network of stakeholders within the health care sector and beyond to generate state-of-the-art science with the intention to support rapid revision of policies and their implementation. Our work is divided into themes corresponding to the strategic research agenda of JPI-AMR, i.e. diagnostics, surveillance, transmission, environment, therapeutics and interventions. We will, when relevant, focus on resistance to carbapenems within each theme. CARe will provide opportunities for and stimulate internal and external collaborations as well as education, outreach and international engagement. The ultimate vision of CARe is to limit mortality, morbidity and socioeconomic costs related to antibiotic resistance on a global scale through research. Please visit CARe's website to read more.

 

The spread of sewage sludge on farmland – long term effects on soils and crops and effects on antibiotic resistance


Project funded by Svenskt Vatten Utveckling during 2017-2018. The project is coordinated by Hushållningssällskapet Skåne and the Larsson group is responsible for the antibiotic resistance research. (475,000 SEK). PI: Joakim Larsson.

Field trials with sewage sludge application on arable land in southwestern Sweden are ongoing since 1981, and these trials are thereby unique in the world. The goal is to evaluate and quantify the effects of applied nutrients, metals, trace elements and humus forming substances. The results from the trials have contributed significantly to the current knowledge about long term effects of sludge application on soil as well as crops. Within the context of the long term field trials, a dedicated study will now be performed on the possible presence of antibiotics, antibiotic resistant bacteria and antibiotic resistance genes in sludge and sludge-fertilized soil. This study, funded by Svenskt Vatten Utveckling 2017-2018 will be performed by the Larsson group at CARe, employing both cultivation-based approaches as well as next generation sequencing of complex communities. The overall project is coordinated by Hushållningssällskapet, Skåne.


Antibiotic Resistance in Wastewater: Transmission Risks for Employees and Residents around Waste Water Treatment Plants (AWARE-WWTP)

Project funded by JPI-AMR with 1.443.354 € during 2017-2020 (36 months). The project is coordinated by RIVM (Ana-Maria de Roda Husman) with partners from Sweden (UGOT, i.e. the Larsson group), Germany (Ludwig-Maximilians-Universität) and Romania (University of Bucharest). The Swedish Research Council VR provides the funding for the Larsson group (4.7MSEK).

The rise of antibiotic resistant infections is an imminent global public health threat, and mitigation measures are required to minimize the risks of transmission and human exposure. Municipal wastewater treatment plants (WWTPs) are known hotspots for the dissemination of clinically relevant resistant bacteria of human origin to the environment, and simultaneously represent targets for intervention and mitigation strategies. While aerosolized bacteria are found within WWTP, it is largely unknown whether WWTP workers are at risk of elevated resistance carriage. In order to study the occupational and environmental transmission of antibiotic resistance due to human exposure to WWTP-borne bacteria, we will assess carriage of extended-spectrum betalactamase (ESBL) and carbapenemase-producing Enterobacteriaceae and resistance genes in WWTP workers, in residents in the proximity of treatment plants, and in water and air samples – both in countries with low and high antimicrobial resistance (AMR). Based on microbial cultivation as well as on high-throughput sequencing data and quantitative real-time polymerase chain reaction (qPCR), exposure through ingestion and inhalation will be modelled, and airborne exposure will be derived from geospatial analyses. Further, we will analyse treatment efficiencies of different WWTP processes in terms of AMR reduction, and therewith identify science-based critical control points for interventions. The focus of this transnational collaboration combining complementary and synergistic European research strengths, is to tackle the increasingly relevant public health threats from antibiotic resistance in WWTP by identifying transmission routes, means of exposure, and proposing risk reduction measures.



The role of antibiotics in the environment for the emergence, selection and transfer of antibiotic resistance

Project funded jointly by the Swedish Research Council VR (Medicine and Health) (0.7 MSEK/year) and the Swedish Research Council FORMAS (1 MSEK/year) for the period 2016-2018.

Harmless environmental bacteria serve as sources for antibiotic resistance genes and resistance plasmids that over time are recruited into human pathogens through horizontal gene transfer. There is a widespread concern that very low, environmental levels of antibiotic residues, derived from human usage, exert selection and increase the risks for such transfers events. In some contrast to this concern, we conclude that there is still very limited scientific evidence supporting this risk scenario. By defining concentrations that select for resistance and drive gene transferin complex microbial communities, we will investigate if resistance promotion primarily, or even only, takes place at higher environmental antibiotic concentrations reached through other routes than via human excretions, such as pollutionfrom antibiotic manufacturing. We will also investigate if industrial pollution with antibiotics promotes the emergence of previously unknown resistance factors. We expect the results to significantly improve our scientific understanding of the role of antibiotics in the environment in the emergence, selection and transfer of antibiotic resistance. Importantly, the research will aid in scaling and directing countermeasures to where they are likely to have an impact, and thereby benefit public health in the long term.



Resistance surveillance via analyses of hospital effluents

Resistance surveillance via analyses of sewage effluents
Research project supported by regional ALF-funding, i.e. funding for clinical research from the Västra-Götalands regionen (VGR). The project is funded with 0.75 MSEK per year between 2018 and 2020. The application group consisted of Joakim Larsson (Biomedicine), Christina Åhrén (VGR), Erik Kristiansson (Chalmers) and Carl-Fredrik Flach (Biomedicine). The collaboration with the local Strama-organization (Swedish Strategic Program against Antibiotic Resistance), Durban University of Technology (South Africa), University of Kenya and Umeå University are important for the project.
Sewage samples can be seen as pooled feces samples from a large number of individuals. Surveillance of resistance in fecal bacteria from sewage could therefore be a highly resource-efficient way to rapidly generate clinically relevant resistance data in parts of the world where traditional, clinical surveillance data is lacking of very sparse. In countries with an established clinical surveillance system (such as Sweden), we believe that complementary sewage surveillance could allow more rapid detection of new resistance threats and outbreaks.



NoCURE: Novel Carbapenemases – UnRaveling the Enviromental reservoir

Framework project funded by the Swedish Research Council VR 2014-2017 with 11.4 MSEK. NoCure is led by Joakim Larsson in collaboration with Erik Kristiansson (Chalmers) and Örjan Samuelsen (University Hospital of North Norway).

The transfer of carbapenem resistance genes from harmless environmental microorganisms or human and animal commensals to pathogenic bacteria threatens the use of our last line of de-fense antibiotics. In this project, we will identify novel carbapenemase candidates using e.g. computational predictions of fragmented metagenomic DNA, functional metagenomics, and plasmid capture experiments. We will then characterize their structure, resistance and mobility potential. The research aims to increase our basic understanding of carbapenemases, including their abundance, diversity and transfer mechanisms. It will also address the patterns of co-resistance between carbapenems and other antibiotics and thereby enable more sustainable treatment strategies to avoid development of multi-resistant pathogens. Our results will also provide input to the evaluation and development of novel carbapenems or other antibiotic molecules less prone to resistance problems in the future.

 


InSiDER – Invasion Success Determinants in bacteria and the Environmental Resistome

Research project funded by the Swedish Research Council FORMAS (3 MSEK) for the period 2017-2020. DNA sequencing is funded by the SciLifeLab Swedish Biodiversity Program (0.85 MSEK).

The project is coordinated by Johan Bengtsson-Palme (Biomedicine) and involves Prof. Joakim Larsson (Biomedicine) and Prof. Jo Handelsman (University of Wisconsin - Madison, USA).

Environmental bacteria host a wide diversity of genes that can confer resistance to antibiotics, which can constitute a source of resistance to human pathogens. This project uses high-throughput sequencing techniques to identify genes improving colonization and invasion ability – or resistance to invasion – in microbial communities under exposure to sub-lethal antibiotics concentrations. To achieve this, we use an experimental system constructed by Prof. Jo Handelsman, and large-scale sequencing of transposon mutants. The project will contribute important knowledge towards the understanding of microbial ecosystem interactions and highlight disturbances to the interactions in microbial communities caused by anthropogenic antibiotic exposure. The genes identified as important for invasion may include novel antibiotic resistance factors, potentially exploiting unknown resistance mechanisms, which could make their way into pathogens in the future. The results of the project will allow for prediction of secondary effects of antibiotic exposure and better prepare us for future challenges related to infections with resistant bacteria.

 


Developing a Framework for Wastewater Reuse in Canada: Using Quantitative Microbial Risk Assessment, Risk Communication, and Community Engagement for Evaluating Water-Fit-For-Purpose Reuse

Project funded by the Canadian Institutes of Health Research to the University of Alberta, CA (Prof Nicholas Ashbolt) 2017-2021 with 2.1 Million CAD. The Larsson group is participating in the project with regards to antibiotic resistance research.
Drinking water treatment and sanitary waste management are considered the most important environmental public health achievements for infectious disease prevention. However, population growth, loss of environmental services and climate change are forcing communities to explore opportunities that treat municipal wastewater to allow its safe return for community uses or harvest rain/stormwater for various non-drinking water uses (all referred to here as wastewater reuse). There are also multiple synergies when wastewater reuse is considered within a broader, one-water approach that provides economic opportunities for society to reduce water service costs, provide resiliency to floods/droughts and promotes public health improvements while meeting future water demands. While wastewater reuse has been accepted in various arid, warm regions (including Arizona, California, Israel & Australia), Canada's cold climate poses uncharacterized challenges to wastewater treatment (e.g. sudden cold-water snowmelt events reducing treatment efficacy) and therefore uncertainty in the potential risks to human health posed by the recovered water. There is also a lack of international agreement on reuse guidelines/regulations that are protective of human health. Lastly, informed citizens are increasingly aware of new disease-causing agents produced by modern societies (e.g., antibiotic-resistant bacteria and respiratory pathogens that grow in distributed waters such as Legionella) and seek to engage in decision-making for new water services. Hence, water reuse strategies require an understanding of the public's perceptions and receptivity to wastewater reuse as well as technical understanding of how to control key hazards - major elements of the proposed participatory water reuse framework to engender trust in government and utilities to provide safe reuse water that communities seek to have in an equitable way to address Canada's $90 billion water service infrastructure deficit.



Halting Environmental Antimicrobial Resistance Dissemination (HEARD)

HEARD is a project funded by the US National Science Foundation (2 million USD 2015-2020) with strong international collaboration, focusing on quantifying the role that wastewater treatment plays in global dissemination of antimicrobial resistance. HEARD brings together experts in environmental microbiology, environmental chemistry, and environmental engineering in an effort to address this global threat.
The project is coordinated by Peter Vikesland and Amy Pruden at Virginia State University, but the partnership spans the globe with members in the United States, China, India, Portugal, the Phillipines, Sweden (Joakim Larsson) and Switzerland.

 

Summary of previous projects

 

 

2013-2017. FORMAS. INTERACT - The interaction of metals and biocides with the selection of antibiotic-resistant bacteria. 25 MSEK. INTERACT is led by Joakim Larsson in collaboration with professors Dan Andersson (UU), Hans Blanck (GU) and Mats Tysklind (UmU).

2016-2017. Swedish Agency for Marine and Water Management. Evaluation of advanced treatment of sewage effluent in full scale. Research project funded with 4,032,000 SEK to UmU, KTH, SLU and GU for year three and four of the project period.

2015. University of Gothenburg. Planning grant for an application to establish an interdisciplinary Centre For Antibiotic Resistance Research at UGOT. 0.5 MSEK.

2015. Swedish Agency for Marine and Water Management. Evaluation of advanced treatment of sewage effluent in full scale.Research project funded with 3,000,000 SEK to UmU, KTH, SLU and GU for year two of the project period.

2015-2017. Regional ALF-funding: Resistance surveillance via analyses of hospital effluents. 2,600,000 SEK to JL.

2014-2018. Sahlgrenska Academy, UGOT. On the recruitment of antibiotic resistance determinants from environmental bacteria to human pathogens. 70% funding for PhD student to JL.

2014. Swedish Agency for Marine and Water Management. Evaluation of advanced treatment of sewage effluent in full scale.
Research project funded with 2,480,000 SEK to UmU, KTH, SLU and GU for year one of the project period.

2014-2017: VR. NoCURE: Novel Carbapenemases – UnRaveling the Enviromental reservoir. 11,400,000 SEK to JL.

2012-2017: FORMAS. Funding for a strong research environment. INTERACT - The interaction of metals and biocides with the selection of antibiotic-resistant bacteria. 25,000,000 SEK to JL.

2012-2015. VR (medicine and health). Personal grant providing a senior scientist position in “Translational Pharmacology” with a focus on “Pharmaceutical pollution – antibiotic resistance development and mode-of-action based test strategies”. 3,804,000 SEK to JL.

2012-2015. MISTRA. MistraPharma - Identification and reduction of environmental risks caused by human pharmaceuticals. 52,000,000 SEK. JL is one of 8 partners in the application group.

2012-2015. Gothenburg Centre for Marine Science Antibiotic resistance in marine bacteria - The role of biocides and metals in the marine environment for promoting and maintaining antibiotic resistance. Funding for two interdisciplinary pair-PhD students to JL (Sahlgrenska Academy) and Hans Blanck (Science Faculty).

2012-2016. FORMAS – strong research environment. NICE – Novel Instruments for effect-based assessment of Chemical pollution in coastal Ecosystems. The program, coordinated by Dr Thomas Backhaus, involves 12 partners from the Gothenburg region. The JL group is mainly involved in work on bacterial metagenomics. 25,000,000 SEK.

2012-2015. VR (natural and engineering sciences). Characterization of antibiotic resistance in bacterial communities: novel methods using next generation sequencing. 3,200,000 SEK. Project grant to Erik Kristiansson (JL is one of three co-applicants).

2012-2015. VR (natural and engineering sciences). Novel methods for improved statistical inference in quantitative metagenomics. 3,600,000 SEK. Project grant to Erik Kristiansson (JL is one of four co-applicants).

2012-2013. LUA-ALF. Multi-drug-resistant Gram-negative infectious bacteria: new genotypic and phenotypic developments for diagnostics and epidemiological control within the clinical environment. 1,600,000 SEK. Project grant to Edward B Moore (JL is one of several co-applicants).

2011-2013. FORMAS. Does a high level of antibiotic pollution increase risks for mobilization of resistance genes from the environment to the human microflora - exploratory studies including deep sequencing. 5,500,000 SEK.

2011-2013. VR (medicine and health). Antibiotic resistance in the external environment - the role of antibiotic pollution in the selection of resistance and subsequent gene transfer to the human microbiome. 1,800,000 SEK. Project grant.

2009-2012 (2015). VR (medicine). Senior scientist in “translational pharmacology” 3 years (3,255,000 SEK) with possibilities to extend 3 years, plus 1,000,000 SEK starting grant for an application on “Pharmaceutical pollution – antibiotic resistance development and mode-of-action based test strategies”.

2009-2012. BONUS (Baltic Organization Network for Funding Science). BALCOFISH - Integration of pollutant gene responses and fish ecology in Baltic coastal fisheries and management. 1,627,763 EURO. JL is one of 7 principal investigators.

2009-2011. SIDA. Microbial diversity and development of antibiotic resistance associated with industrial wastewater treatment. 750,000 SEK to ERB Moore (JL co-applicant).

2008-2012. Göteborg Research School for Environment and Health. Consumption of inexpensive medicines – increased risks for resistance development and environmental effects? 1,800,000 SEK to JL.

2008-2011. MISTRA. MistraPharma – identification and reduction of environmental risks caused by the use of human pharmaceuticals. 44,200,000 SEK. JL is one of seven partners in the application group.

2008-2010. FORMAS. Endocrine disruption of non-genomic progesterone signaling - consequences for gamete transport and sex ratios. 2,587,950 SEK to JL.

2008-2010. Swedish Environmental Protection Agency and MISTRA. Swedish field studies to evaluate ecotoxicological effects of pharmaceuticals in sewage effluents. 438,000 SEK to JL.

2008-2009. Stockholm Vatten. Fortsatta fiskförsök för att utvärdera reningsmetoder som avlägsnar läkemedelsrester. 479,900 SEK to JL.

2007-2009. FORMAS. Multi-Endpoint Microarray Analyses in Biological Effect Monitoring of Wild Fish Populations. 3,280,500 SEK to L Förlin and J Larsson.

2007-2011. GU (Science faculty – strategical area). Ecotoxicology – from gene to ocean. 12,500,000 SEK. J Larsson co-applicant with L Förlin, H Blanck, G Dave and M Celander.

2007-2008. Adlerbertska Research Foundation. Assessing the risks for bacterial resistance development in effluents from Indian pharmaceutical industries 135,000 SEK

2006-2007. SIDA. Studies of the effluent toxicity from the Patancheru Enviro-Tech Ltd plant in Hyderabad, India to direct further actions including possible mitiations. 231,000 SEK to JL.

2006-2007. MISTRA. Planning grant for a research program application on Pharmaceuticals in the Environment. 300,000 SEK to KTH, GU, UmU, SU and Kemi&Miljö.

2006-2010. GU (Science faculty – strategical area). Göteborg Research platform on Integrative Physiology (GRIP). 14,000,000 SEK. Coordinator S. Holmgren (24 principal investigators).

2006-2007. FORMAS. Pharmaceuticals in the Environment – Development of Biological Fingerprints. 1,000,000 to JL

2005-2006. VA-FORSK. Analysesof pharmaceutical residues in fish blood for evaluation of environmental effects of sewage effluents. 358,600 SEK to JL.

2004-2007. MISTRA. Pharmaceuticals in the Environment Development of Biological Fingerprints. 1,670,000; 1,730,000; 1,660,000 and 2,310,000 SEK to JL

2005-2006. Swedish Research Council (VR-Medicine). Project grant. Project K2005-72X-14572-03A to JL: How does progesterone control programmed cell death – specific roles of membrane progesterone receptors. 225,000 SEK per year

2004-2005. FORMAS. Pharmaceuticals in the Environment – Development of Biological Fingerprints. 1120,000 and 1050,000 SEK to JL.

2003-2004. Adlerbertska Research Foundation. Pharmaceuticals in the Environment – development of biological fingerprints. 50,000 SEK to JL.

2003. GUVR (Göteborg University Science Council). Interdisciplinary project planning grant: Environmental effects of pharmaceuticals. 50,000 SEK to JL.

2003-2006. Swedish Research Council (Medicin). Position as Assistant Professor. Project 2003/B1664 to JL. 643,000 SEK per year

2003-2004. Swedish Research Council (Medicin). Special funding for young scientists. Project 2003/B0828 to JL: How does progesterone control programmed cell death? 208,000 SEK per year

2003-2004. Swedish Research Council (Medicin). Bioscience project 2003/B0828B to JL: How does progesterone control programmed cell death? 52,000 SEK per year

2002. FORMAS (The Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning). Disturbed sex ratios in aquatic organisms exposed to pulp mill effluents. Co-investigator. 520,000 SEK.

2001. MISTRA (Foundation for Strategic Environmental Research). Sublethal effects of endocrine disrupters in fish. Co-investigator. 400,000 SEK.

2001. Swedish Environmental Protection Agency. What causes masculinization and other endocrine disturbances in fish downstream pulpmills? Co-investigator. 350,000 SEK.

2000-2001. Södra Cell. Studies of endocrine changes in fish in the recipient from Mönsterås bruk. Principal Investigator. 190,000 SEK.

2000. MISTRA. Sublethal effects of endocrine disrupters in fish. Co-investigator. 400,000 SEK.

2000. Swedish Environmental Protection Agency. What causes masculinization and other endocrine disturbances in fish downstream pulpmills? Co-investigator. 300,000 SEK.

1999-2000. Södra Cell. Studies of endocrine changes in fish in the recipient from Mönsterås bruk. Co-investigator. 550,000 SEK.

1999. MISTRA Sublethal effects of endocrine disrupters in fish. Co-investigator. 400,000 SEK.

Interview with Joakim Larsson, Institute of Biomedicine at University of Gothenburg, about the UN Sustainable Development Goal number 3: Good Health and Well-being.

Sidansvarig: Dan Baeckström|Sidan uppdaterades: 2019-02-01
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