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Carl-Fredrik Flach


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Guldhedsgatan 10
41346 Göteborg
Su sahlgrenska
41345 Göteborg

Om Carl-Fredrik Flach

Ongoing projects:

Transmission of antibiotic resistance plasmids in sewage The project is funded by the Swedish Research Council FORMAS (3 MSEK) for the period 2019-2021 and led by Carl-Fredrik Flach. The rise of antibiotic-resistant bacterial pathogens is a major threat to public health. Environmental bacteria play an important role by providing a source of antibiotic resistance genes that can be horizontally transferred to pathogens, which often involves the acquisition of resistance plasmids. Sewage environments, harboring a mixture of environmental and pathogenic bacteria as well as resistance plasmids have been pointed out as hotspots for such development. This project will assess the inductive effect of the complete mixtures of antimicrobials present in different types of sewage (raw hospital and municipal as well as treated sewage) on plasmid transfer in bacterial sewage communities. We will also determine how pre-carriage of different plasmids affect acquisition of additional plasmids and map dissemination of transferred plasmids in the sewage communities. The project is expected to provide guidance for the decision-making process whether, and if so where, additional treatment of sewage should be implemented regarding the risk for antibiotic resistance dissemination.

Resistance surveillance via analyses of hospital sewage Research 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), Carl-Fredrik Flach (Biomedicine), Christina Åhrén (VGR) and Erik Kristiansson (Chalmers). 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. Comparisons will be made with patient screening cultures and clinical isolates as well as local antibiotic use.

Expanding resistance surveillance via analyses of sewage to low income countries Research supported by CARe with 1.24 MSEK from 2018-2020. The project is led by Carl-Fredrik Flach. Collaborations with Durban University of Technology, Technical University of Kenya and Umeå University are important for the project. This project builds on the experiences from the regional ALF-project on hospital effluent described above, but aims to apply and transfer the technology to other countries, particularly those where regional surveillance systems are weak. Thanks to international collaborations, we will sample and analyze raw sewage water across sub-Saharan Africa in order to get a picture of the antibiotic resistance situation in human populations in a region of the world where clinical surveillance is very limited.

The role of sewage in emergence, selection, dissemination and surveillance of antibiotic resistant bacteria 70% funding for a PhD student from Sahlgrenska Academy, University of Gothenburg, to Carl-Fredrik Flach 2017-2021. Marion Hutinel was appointed the PhD student position.

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. We aim to: 1. Understand the origin and evolution of antibiotic resistance genes, 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.

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). 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.


Previous projects, short summary:

Antibiotic resistant bacteria in sewage and dissemination to the environment The project was funded by the Swedish Research Council FORMAS (4.6 MSEK) for the period 2015-2017 and led by Carl-Fredrik Flach.

The role of antibiotics in the environment for the emergence, selection and transfer of antibiotic resistance Research 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. The project was coordinated by Joakim Larsson. Carl-Fredrik Flach, Jerker Fick (Umeå University) and Erik Kristiansson (Chalmers) were co-applicants.