Carl-Fredrik Flach

Researcher

Department of Infectious Diseases

Mail

carl-fredrik.flach@microbio.gu.se

Visiting address

Guldhedsgatan 10

41346 Göteborg

Postal address

Su sahlgrenska

41345 Göteborg

About Carl-Fredrik Flach

Ongoing funded projects:

Sewage monitoring – a new, resource-efficient method for population-based surveillance of antibiotic resistance The project is funded by the Wellcome Trust (10.2 MSEK) for the period 2022-2025. The research is led by Carl-Fredrik Flach. Collaboration with Prof Joakim Larsson (University 91̽��), Prof Sabiha Essack (University of KwaZulu-Natal, South Africa), Dr Inacio Mandomando (Manhica Health Research Centre, Mozambique) and Dr Patrick Okanya (Technical University of Kenya). Antibiotic resistance surveillance is critical for guiding empirical treatment and evaluating interventions. As current methods rely on analyses of bacterial isolates from many individuals, surveillance is resource-demanding and thus absent or very limited in most low- and middle-income countries (LMICs). We hypothesize that microbiological analyses of sewage, containing excreted bacteria from thousands of people, can be a resource-efficient complement for population-level antibiotic resistance surveillance with particular value in LMICs. This is supported by our recent European studies showing good correlation between resistance rates in clinical and sewage E. coli isolates. Here we aim to further develop the sewage monitoring system by targeting additional clinically important bacteria in sewage and investigating the value of including gene-based analyses. We also aim to validate the methodology in three sub-Saharan African countries by benchmarking to local clinical surveillance data generated during the project. The relationship between sewage and clinical ESBL-producing strains, one of the most urgent resistance threats, will be studied in more detail by applying whole genome sequencing. By also engaging relevant stakeholders, the overarching goal is to pave the way for future implementation of sewage monitoring, which could significantly increase the basic data for surveillance of antibiotic resistance in LMICs.

Antibiotic resistance genes in wastewater – studies on factors critical for assessing the risks. The project is funded by the Swedish Research Council FORMAS (3 MSEK) for the period 2022-2024 and led by Carl-Fredrik Flach. Antibiotic resistance genes (ARGs) can be present in both pathogens and harmless environmental bacteria. The acquisition of ARGs, often situated on plasmids, by pathogens and their subsequent spread represent a major threat to human health. Wastewaters have been pointed out as risk environments for development of resistant pathogens as well as for their dissemination to the environment, from where they can reach humans and cause infections. Wastewaters are often analyzed with regard to ARG content in order to assess risks. Although applied methodologies can be both comprehensive and efficient, they are hampered by an inability to link the detected ARGs to their bacterial hosts. Knowledge about which bacteria are carrying the ARGs is however critical for assessing risks. Additionally, if pathogens carry certain plasmids it might facilitate the acquisition of others, but if this affects acquisition of ARGs in wastewaters is still unknown. This project will therefore address the following questions: (1) Which ARGs are disseminated to the environment via wastewater in Sweden. (2) Which are re the bacterial hosts of the ARGs present in wastewater? (3) Does pre-carriage of plasmids in pathogens promote acquisition of ARGs in wastewater? The project will fill those knowledge gaps by advancing recently applied methodologies and is thereby expected to generate results and methods important for i) assessing risks regarding ARGs in wastewaters and ii) evaluating mitigating measures.

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 91̽��), 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.

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. 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.

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