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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 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

Research project supported by regional ALF-funding, i.e. funding for clinical research from the Västra-Götalands regionen. The project is funded with 0.85 MSEK per year between 2015 and 2017. The application group consisted of Joakim Larsson (Biomedicine), Christina Åhrén (Strama), Erik Kristiansson (Chalmers) and Carl-Fredrik Flach (Biomedicine). The collaboration with the local Strama-organization (Swedish Strategic Program against Antibiotic Resistance) at three major hospitals in the region (SU, SKAS, SÄS) is a very important for the project.

Sewage samples can be seen as pooled feces samples from a large number of individuals. As a complement to traditional patient-based screening, effluent-screening therefore has a potential to rapidly identify trends in the resistance situation to a low cost. Such information can provide input to changes in recommendations of antibiotics use as well as initiate measures to limit dissemination. In this project we will develop and evaluate methods (culturing, metagenomics, PCR, plasmid capture) to quantify selected resistant pathogens, resistance genes and resistance plasmids. Comparisons will be made with patient screening cultures and clinical isolates as well as local antibiotic use.

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.
 

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

Strong Research Environment funded by FORMAS 2012-2016 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.
 

Pharmaceutical pollution – antibiotic resistance development and mode-of-action based test strategies

Senior scientist position for Joakim Larsson 2009-2015 within the field of Translational Pharmacology including a startup-grant from the Swedish Research Council (Medicine).
This grant covers research on several aspects on environmental effects of pharmaceuticals where there currently are major knowledge gaps. My group will focus on three areas:

  1. assess risks (including resistance development) associated with the extaordinary large releases of antibiotics and other pharmaceuticals from bulk drug producers in India
  2. identify drugs likely to cause environmental effects and contribute to a scientifically founded framework for mode-of-action based environmental risk assessments of human pharmaceuticals
  3. evaluate effluent treatment technologies to reduce the environmental impact of pharmaceuticals

 

MistraPharma - Identification and reduction of environmental risks caused by human pharmaceuticals (phase II).

Research program supported by the Swedish Foundation for Strategic Environmental Research (MISTRA) 2012-2015 with 52 MSEK. The program involves partners at the Sahlgrenska Academy at University of Gothenburg, Chalmers University of Technology, the Royal Institute of Technology, Uppsala University, Stockholm University, Umeå University, Brunel University (UK) and Stella Futura. Programme website: www.mistrapharma.se

The major aims of this interdisciplinary research program are to:

(1) Identify high risk APIs
By generating new data with high relevance in environmental risk management
(2) Understand promotion of antibiotic resistance in the environment
By determining antibiotic resistance factors in contaminated environments and assessing different selection pressures
(3) Evaluate removal of high risk APIs through wastewater treatment
By assessing the feasibility of ozonation and/or activated carbon in wastewater treatment
(4) Contribute to the development of improved risk management
By improving the scientific basis for environmental classification, risk assessment and substitution
(5) Provide state-of-the-art analyses of APIs of environmental concern
By developing and quality assuring analytical methods
(6) Provide decision support to stakeholders
By communicating generated knowledge to ensure that it can be put to practical use.
 

Antibiotic resistance in marine bacteria - the role of biocides and metals in the marine environment for promoting and maintaining antibiotic resistance

Funding for two PhD student from the Gothenburg Centre for Marine Research 2012-2015 to Joakim Larsson and Hans Blanck

One of the primary goals for Gothenburg Centre for Marine Research is to coordinate marine environmental research in Gothenburg and to bring together scientists from different disciplines. This interdisciplinary project combines competence from the Health Faculty and the Natural Science Faculty to address potential drivers for the development of antibiotic resistance, one of the most urgent threats to human health globally. Bacteria often carry resistance elements to metals and biocides together with resistance elements to antibiotics. Thus, a selection pressure from metals and biocides may select also for antibiotic resistance. By combining our competences in large-scale DNA sequencing and bacterial biofilm ecology, this project will address the risks for the promotion of antibiotic resistant bacteria, through indirect selection pressures, in the marine environment.  

 

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) 2012-2016 with 25 MSEK. 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.

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.
 

Characterization of antibiotic resistance in bacterial communities: novel methods using next generation
sequencing

Project grant from the Swedish Research Council (VR-NT) 2012-2015 to Erik Kristiansson (DGJ Larsson, ERB Moore and G Kemp are co-applicants).

The accelerated development of antibiotic resistance is one of the most urgent threats to human health. Bacteria become resistant to antibiotics by acquiring resistance genes through the process of horizontal gene transfer. Since antibiotics are naturally produced by many organisms, environmental bacterial communities contain a particular high diversity of resistance genes. Understanding the role of the environment as a reservoir for resistance genes and their routes of transfer is therefore vital. In this project we will develop novel tools for explorative analysis of resistance genes in bacterial communities. The tools are based on data generated by the next generation DNA sequencing and have therefore a high sensitivity and precision, even for less abundant genes. We will also develop tools for culture-independent characterization of resistance plasmids, which are the main vehicles for transmission of resistance genes between bacterial cells. The methods will be used to analyze data from environmental bacterial communities, both with and without antibiotic selection pressure, and the human microbiome. The project will generate novel insights into the development, promotion and spread of antibiotic resistance. The methods will have a great applicability in both basic and clinical microbiology as well as in metagenomics in general.
 

Novel methods for improved statistical inference in quantitative metagenomics

Project grant from the Swedish Research Council (VR-NT) 2012-2015 to Erik Kristiansson (DGJ Larsson, O Nerman, T Backhaus and H Blanck are co-applicants).

In metagenomics communities of microorganisms are studied by observing random fragments of their genomes. The potential of metagenomics have increased with the introduction of next generation DNA sequencing and it constitutes today an important measurement technique in ecology, ecotoxicology and medicine. Metagenomics is however limited by high levels of technical and biological noise, the low number of samples and the high dimensionality of the observed data. In this project we will develop novel statistical methods for analysis of gene count abundance in metagenomes. We will model the complex structure of metagenomics data and develop robust estimators for the biological variation between metagenomes. We will also develop new methods for normalization of metagenomes with varying taxonomic composition. The methods will be applied in three collaborative research projects where metagenomics is an essential measurement technique. The methods will also be implemented in a software package that will be freely available for the microbiology research community. The statistical methodology developed within this project will improve the performance of metagenomics and thus the study of uncultured microorganisms in general.
 

 

Kontaktinformation

Joakim Larsson

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

Besöksadress:
Guldhedsgatan 10a, 5th floor

Telefon:
+46 (0) 31 342 4625

Sidansvarig: Dan Baeckström|Sidan uppdaterades: 2016-05-18
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