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Prof Joakim Larsson











Summary of funded projects

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 and Fredrik Carlsson are main applicants, and in total 30 principal investigators from six faculties and three core external partners are engaged in the centre (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. 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.

Evaluation of advanced treatment of sewage effluent in
full scale

Research project funded by the Swedish Agency for Marine and Water Management with 9.512 MSEK for 2014-2017. The application group consisted of Jerker Fick (Umeå university, main project leader), Berndt Björlenius (Royal Institute of Technology), Leif Norrgren (Swedish University of Agricultural Sciences) and Joakim Larsson (University of Gothenburg). Additional project-partners include Knivsta Reningsverk, Roslagsvatten and Tomas Brodin (Umeå University).

In this project we will implement ozonation as a method to remove pharmaceuticals, microbes and other micro-pollutants from sewage effluents. Ozonation will be implemented on full scale at a Swedish sewage treatment plant in Knivsta. This will provide us with valuable experience from practical implementation at full scale. We will also evaluate the removal of 120 pharmaceuticals, other micropollutants and microbes from the effluent. We will follow several upstream and downstream sites in the receiving river before, during and after the ozonation period in order to evaluate the effects of ozonation on the river microbial communities (including antibiotic-resistant bacteria), fish and invertebrate communities.

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.


INTERACT - The interaction of metals and biocides with the selection of antibiotic-resistant bacteria

Strong Research Environment funded by FORMAS 2013-2017 with 25 MSEK. INTERACT is led by Joakim Larsson in collaboration with professors Dan Andersson (UU), Hans Blanck (GU) and Mats Tysklind (UmU). Programme website: www.interact.gu.se

Multi-resistant bacteria cause tens of thousands of deaths every year in Europe, jeopardizing all kinds of medical procedures. According to the WHO, the rapid resistance development is one of the largest threats to public health, globally. Alarmingly, not only antibiotics select for resistance, but the combined exposure to biocides and metals can also contribute through co-selection and cross-resistance. Chemicals in the environment may thus make bacteria untreatable with antibiotics at a later stage. To enable mitigations, INTERACT will identify chemicals and environments associated with high risks for combination effects. Specifically, we will assess:

  1. What biocides and concentrations that promote resistance development
  2. In which environments high-risk mixtures can be found
  3. The genetic basis for co- and cross-resistance
  4. The potential for resistance factors to spread from the environment to human pathogens

INTERACT is expected to provide crucial input to environmental regulatory agencies, as well as the health care, water and shipping sectors.

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.


NICE – Novel Instruments for effect-based assessment of Chemical pollution in coastal Ecosystems

Strong Research Environment funded by the Swedish Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS) 2012-2018 with 25 MSEK. The program, coordinated by Dr Thomas Backhaus, involves 12 partners from the Gothenburg region. The JL group is involved in work on fish ecotoxicology.

Mixtures of toxic chemicals regularly occur in our coastal ecosystems. NICE develops instruments for monitoring their ecological effects, as required by the Water Framework Directive and needed for identification of the relevant pollutants in the field. The NICE tools will be evaluated in field studies. We will suggest options for environmental regulation of chemical mixtures, thus providing input to the water management in Västra Götaland. Reference and contaminated sites mainly on the Swedish coast will be selected in co-operation with stakeholder authorities and subjected to deeper ecotoxicological investigations. Chemical monitoring data will initially be used for pinpointing the pollutants at each site. These will be ranked according to their expected environmental impact and then further investigated by extended chemical analysis. Ecotoxicological effect profiles ("fingerprints") of the priority pollutants will be recorded for microbial communities, invertebrates and fish, using classic biomarkers, population level endpoints, ecological effect indicators (PICT) and advanced fingerprints based on (gen-)OMICs. The fingerprints will be used to detect effects in the environment, providing causal links between the mere presence of pollutants and their ecological impact of a site. The effect profiles will be aggregated into models for site-specific ecological impacts, which will be amended, if needed, to take into account the presence of unknown pollutants and interactions.



Joakim Larsson

Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Guldhedsgatan 10, SE-413 46, Göteborg

Guldhedsgatan 10a, 5th floor

+46 (0) 31 342 4625

Sidansvarig: Dan Baeckström|Sidan uppdaterades: 2018-01-25

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