Carl-Fredrik Flach
About Carl-Fredrik Flach
Ongoing projects:
Antibiotic resistant bacteria in sewage and dissemination to the environment The project is funded by the Swedish Research Council FORMAS (4.6 MSEK) for the period 2015-2017 and led by Carl-Fredrik Flach. Sewage environments have been identified as risk environments for the development and transmission of antibiotic resistant bacteria. In order to reduce risks, both pre-treatment of hospital sewage as well as add-on treatment techniques at sewage treatment plants are discussed in Sweden and elsewhere. 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, this project will address the following questions; 1) Which major antibiotic resistance threats are present in treated sewage in Sweden and to what extent? 2) Are hospitals major contributors the antibiotic resistant pathogens found in municipal sewage treatment plants? 3) What are the risks for transfer of resistance factors to pathogens in municipal, hospital and treated sewage?
Resistance surveillance via analyses of hospital effluents Research 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), Carl-Fredrik Flach (Biomedicine), Christina Åhrén (Strama) and Erik Kristiansson (Chalmers). The collaboration with the local Strama-organization (Swedish Strategic Program against Antibiotic Resistance) at three major hospitals in the region (SU, SKAS, SÄS) is 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.
Expanding resistance surveillance via analyses of sewage to low income countries Research supported by CARe from 2016. The project will involve Carl-Fredrik Flach, Joakim Larsson, Rune Andersson and other PIs from CARe in addition to many international partners. 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. During 2016 we will start working in Kenya (Dr Carl-Johan Svensson) and we plan to expand to several more countries. The plan is to involve medical students during their exam-projects.
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 is coordinated by Joakim Larsson. Carl-Fredrik Flach, Jerker Fick (Umeå University) and Erik Kristiansson (Chalmers) are co-applicants. 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 transfer in 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.
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The association between insertion sequences and antibiotic resistance
genes
Mohammad Razavi, Erik Kristiansson, Carl-Fredrik Flach, D. G. Joakim Larsson
mSphere - 2020-01-01 -
Predicting clinical resistance prevalence using sewage metagenomic
data
Antti Karkman, Fanny Berglund, Carl-Fredrik Flach, Erik Kristiansson, D. G. Joakim Larsson
Communications Biology - 2020-01-01 -
Selective concentrations for trimethoprim resistance in aquatic
environments
Nadine Kraupner, Stefan Ebmeyer, Marion Hutinel, J. Fick, Carl-Fredrik Flach, D. G. Joakim Larsson
Environment International - 2020-01-01 -
Structural insights into the enhanced carbapenemase efficiency of OXA-655 compared to
OXA-10
H. K. S. Leiros, A. M. Thomassen, Samuelsen, Samuelsen,, Carl-Fredrik Flach, Stathis Kotsakis, D. G. Joakim Larsson
FEBS Open Bio - 2020-01-01 -
Long-term application of Swedish sewage sludge on farmland does not cause clear changes in the soil bacterial
resistome.
Carolin Rutgersson, Stefan Ebmeyer, Simon Bo Lassen, Antti Karkman, Jerker Fick, Erik Kristiansson, Kristian K Brandt, Carl-Fredrik Flach, D. G. Joakim Larsson
Environment international - 2020-01-01 -
Surveillance of antibiotic resistant Escherichia coli in human populations through urban wastewater in ten European
countries.
Patricia Huijbers, D. G. Joakim Larsson, Carl-Fredrik Flach
Environmental pollution (Barking, Essex : 1987) - 2020-01-01 -
Discovery of a novel integron-borne aminoglycoside resistance gene present in clinical pathogens by screening environmental bacterial
communities.
Maria-Elisabeth Böhm, Mohammad Razavi, Nachiket Marathe, Carl-Fredrik Flach, D. G. Joakim Larsson
Microbiome - 2020-01-01 -
A novel, integron-regulated, class c
β-lactamase
Maria-Elisabeth Böhm, Mohammad Razavi, Carl-Fredrik Flach, D. G. Joakim Larsson
Antibiotics - 2020-01-01 -
Diarrheal bacterial pathogens and multi-resistant enterobacteria in the Choqueyapu River in La Paz,
Bolivia
J. Guzman-Otazo, Lucia Gonzales-Siles, V. Poma, Johan Bengtsson-Palme, Kaisa Thorell, Carl-Fredrik Flach, V. Iniguez, A. Sjoling
PLoS ONE - 2019-01-01 -
Characterization of the first OXA-10 natural variant with increased carbapenemase
activity.
Stathis Kotsakis, Carl-Fredrik Flach, Mohammad Razavi, D. G. Joakim Larsson
Antimicrobial agents and chemotherapy - 2019-01-01 -
Population-level surveillance of antibiotic resistance in Escherichia coli through sewage
analysis
Marion Hutinel, Patricia Huijbers, Jerker Fick, Christina Åhrén, D. G. Joakim Larsson, Carl-Fredrik Flach
Eurosurveillance - 2019-01-01 -
A conceptual framework for the environmental surveillance of antibiotics and antibiotic
resistance.
Patricia Huijbers, Carl-Fredrik Flach, D. G. Joakim Larsson
Environment international - 2019-01-01 -
Antibiotics and common antibacterial biocides stimulate horizontal transfer of resistance at low
concentrations.
Jekaterina Jutkina, Nachiket Marathe, Carl-Fredrik Flach, D. G. Joakim Larsson
The Science of the total environment - 2018-01-01 -
Critical knowledge gaps and research needs related to the environmental dimensions of antibiotic
resistance
D. G. Joakim Larsson, Antoine Andremont, Johan Bengtsson-Palme, K. K. Brandt, A. M. D. Husman, P. Fagerstedt, J. Fick, Carl-Fredrik Flach, W. H. Gaze, M. Kuroda, Kristian Kvint, R. Laxminarayan, C. M. Manaia, K. M. Nielsen, L. Plant, M. C. Ploy, C. Segovia, P. Simonet, K. Smalla, J. Snape, E. Topp, A. J. van Hengel, D. W. Verner-Jeffreys, M. P. J. Virta, E. M. Wellington, A. S. Wernersson
Environment International - 2018-01-01 -
A Comprehensive Screening of Escherichia coli Isolates from Scandinavia's Largest Sewage Treatment Plant Indicates No Selection for Antibiotic
Resistance.
Carl-Fredrik Flach, Maja Genheden, Jerker Fick, D. G. Joakim Larsson
Environmental science & technology - 2018-01-01 -
Functional metagenomics reveals a novel carbapenem-hydrolyzing mobile beta-lactamase from Indian river sediments contaminated with antibiotic production
waste
Nachiket Marathe, Anders Janzon, Stathis Kotsakis, Carl-Fredrik Flach, Mohammad Razavi, Fanny Berglund, Erik Kristiansson, D. G. Joakim Larsson
Environment International - 2018-01-01 -
Selective concentration for ciprofloxacin resistance in Escherichia coli grown in complex aquatic bacterial
biofilms
Nadine Kraupner, Stefan Ebmeyer, Johan Bengtsson-Palme, J. Fick, Erik Kristiansson, Carl-Fredrik Flach, D. G. Joakim Larsson
Environment International - 2018-01-01 -
Does antifouling paint select for antibiotic
resistance?
Carl-Fredrik Flach, Chandan Pal, Carl Johan Svensson, Erik Kristiansson, Marcus Östman, Johan Bengtsson-Palme, Mats Tysklind, D. G. Joakim Larsson
The Science of the total environment - 2017-01-01 -
Identification of 76 novel B1 metallo-beta-lactamases through large-scale screening of genomic and metagenomic
data
Fanny Berglund, Nachiket Marathe, Tobias Österlund, Johan Bengtsson-Palme, Stathis Kotsakis, Carl-Fredrik Flach, D. G. Joakim Larsson, Erik Kristiansson
Microbiome - 2017-01-01 -
Discovery of the fourth mobile sulfonamide resistance
gene
Mohammad Razavi, Nachiket Marathe, Michael Gillings, Carl-Fredrik Flach, Erik Kristiansson, D. G. Joakim Larsson
Microbiome - 2017-01-01 -
Computational discovery and functional validation of novel fluoroquinolone resistance genes in public metagenomic data
sets
Fredrik Boulund, Fanny Berglund, Carl-Fredrik Flach, Johan Bengtsson-Palme, Nachiket Marathe, D. G. Joakim Larsson, Erik Kristiansson
BMC Genomics - 2017-01-01 -
Elucidating selection processes for antibiotic resistance in sewage treatment plants using
metagenomics
Johan Bengtsson-Palme, Rickard Hammarén, Chandan Pal, Marcus Östman, Berndt Björlenius, Carl-Fredrik Flach, Jerker Fick, Erik Kristiansson, Mats Tysklind, D. G. Joakim Larsson
Science of the Total Environment - 2016-01-01 -
Minimal selective concentrations of tetracycline in complex aquatic bacterial
biofilms
Sara Lundström, Markus Östman, Johan Bengtsson-Palme, Carolin Rutgersson, Malin Thoudal, Triranta Sircar, Hans Blanck, Karl Martin Eriksson, Mats Tysklind, Carl-Fredrik Flach, D. G. Joakim Larsson
Science of the Total Environment - 2016-01-01 -
An assay for determining minimal concentrations of antibiotics that drive horizontal transfer of
resistance
Jekaterina Jutkina, Carolin Rutgersson, Carl-Fredrik Flach, D. G. Joakim Larsson
Science of the Total Environment - 2016-01-01 -
Isolation of novel IncA/C and IncN fluoroquinolone resistance plasmids from an antibiotic-polluted
lake
Carl-Fredrik Flach, Anna Johnning, Ida Nilsson, Kornelia Smalla, Erik Kristiansson, D. G. Joakim Larsson
Journal of Antimicrobial Chemotherapy - 2015-01-01 -
Defining the Roles of IFN-gamma and IL-17A in Inflammation and Protection against Helicobacter pylori
Infection
Louise Sjökvist Ottsjö, Carl-Fredrik Flach, Staffan Nilsson, R. D. Malefyt, A. K. Walduck, Sukanya Raghavan
PLoS ONE - 2015-01-01 -
Fluoroquinolones and qnr genes in sediment, well water, soil and human fecal flora in an Indian environment polluted by drug
manufacturing
Carolin Rutgersson, Jerker Fick, Nachiket Marathe, Erik Kristiansson, Anders Janzon, Martin Angelin, Anders Johansson, Yogesh Shouche, Carl-Fredrik Flach, D. G. Joakim Larsson
Environmental Science and Technology - 2014-01-01 -
The role of IL-17A and IFN gamma in vaccine-induced protection against Helicobacter pylori
infection
Louise Sjökvist Ottsjö, Carl-Fredrik Flach, Staffan Nilsson, R. D. Malefyt, A. Walduck, Sukanya Raghavan
Cytokine - 2014-01-01 -
Functional verification of computationally predicted qnr
genes
Carl-Fredrik Flach, Fredrik Boulund, Erik Kristiansson, D. G. Joakim Larsson
Annals of Clinical Microbiology and Antimicrobials - 2013-01-01 -
High levels of quinolone resistance genes found near a waste water treatment plant serving antibiotic
manufacturers
Carolin Rutgersson, Carl-Fredrik Flach, Nachiket Marathe, Erik Kristiansson, Anders Janzon, J. Fick, Y. Shouche, Edward R.B. Moore, D. G. Joakim Larsson
52nd International Conference on Antimicrobial Agents and Chemotherapy (ICAAC), 9-12 September 2012, San Francisco - 2013-01-01 -
A double mutant heat-labile toxin from Escherichia coli, LT(R192G/L211A), is an effective mucosal adjuvant for vaccination against Helicobacter pylori
infection.
Louise Sjökvist Ottsjö, Carl-Fredrik Flach, Jan Holmgren, John Clements, Sukanya Raghavan
Infection and immunity - 2013-01-01 -
Mucosal vaccination increases local chemokine production attracting immune cells to the stomach mucosa of Helicobacter pylori infected
mice.
Carl-Fredrik Flach, Michael Mozer, Malin Sundquist, Jan Holmgren, Sukanya Raghavan
Vaccine - 2012-01-01 -
The subcellular location of antigen expressed by adenoviral vectors modifies adaptive immunity but not dependency on cross-presenting dendritic
cells.
Petra Henning, Tobias Gustafsson, Carl-Fredrik Flach, Yeu-Jiann Hua, Anna Strömbeck, Jan Holmgren, Leif Lindholm, Ulf Yrlid
European journal of immunology - 2011-01-01 -
Interferon-gamma secretion is induced in IL-12 stimulated human NK cells by recognition of Helicobacter pylori or TLR2
ligands
Åsa Lindgren, Voja Pavlovic, Carl-Fredrik Flach, Åsa Sjöling, Samuel B Lundin
Innate Immunity - 2011-01-01 -
A truncated form of HpaA is a promising antigen for use in a vaccine against Helicobacter
pylori.
Carl-Fredrik Flach, Natascha Svensson, Margareta Blomquist, Annelie Ekman, Sukanya Raghavan, Jan Holmgren
Vaccine - 2011-01-01 -
Pro-inflammatory cytokine gene expression in the stomach correlates with vaccine-induced protection against Helicobacter pylori infection in mice: an important role for interleukin-17 during the effector
phase.
Carl-Fredrik Flach, Anna Karin Ostberg, Anne-Therese Nilsson, Rene De Waal Malefyt, Sukanya Raghavan
Infection and immunity - 2011-01-01 -
Sublingual immunization protects against Helicobacter pylori infection and induces T and B cell responses in the
stomach.
Sukanya Raghavan, Anna Karin Ostberg, Carl-Fredrik Flach, Annelie Ekman, Margareta Blomquist, Cecil Czerkinsky, Jan Holmgren
Infection and immunity - 2010-01-01 -
B lymphocytes promote expansion of regulatory T cells in oral tolerance: powerful induction by antigen coupled to cholera toxin B
subunit.
Jia-Bin Sun, Carl-Fredrik Flach, Cecil Czerkinsky, Jan Holmgren
Journal of immunology (Baltimore, Md. : 1950) - 2008-01-01 -
Real-time PCR quantification analysis of five mucosal transcripts in patients with Crohn's
disease.
Anders Eriksson, Eva Jennische, Carl-Fredrik Flach, Alberto Jorge, Stefan Lange
European journal of gastroenterology & hepatology - 2008-01-01 -
Five mucosal transcripts of interest in ulcerative colitis identified by quantitative real-time PCR: a prospective
study.
Anders Eriksson, Carl-Fredrik Flach, Anders Lindgren, Eva Kvifors, Stefan Lange
BMC gastroenterology - 2008-01-01 -
Differential expression of intestinal membrane transporters in cholera
patients.
Carl-Fredrik Flach, Firdausi Qadri, Taufiqur Rahman Bhuiyan, N. H. Alam, Eva Jennische, Jan Holmgren, Ivar Lönnroth
FEBS letters - 2007-01-01 -
Broad up-regulation of innate defense factors during acute
cholera.
Carl-Fredrik Flach, Firdausi Qadri, Taufiqur Rahman Bhuiyan, N. H. Alam, Eva Jennische, Ivar Lönnroth, Jan Holmgren
Infection and immunity - 2007-01-01 -
Detection of elafin as a candidate biomarker for ulcerative colitis by whole-genome microarray
screening.
Carl-Fredrik Flach, Anders Eriksson, Eva Jennische, Stefan Lange, Charina Gunnerek, Ivar Lönnroth
Inflammatory bowel diseases - 2006-01-01 -
Mucosal adjuvants and anti-infection and anti-immunopathology vaccines based on cholera toxin, cholera toxin B subunit and CpG
DNA
Jan Holmgren, Jenni Adamsson, F. Anjuere, J. Clemens, C. Czerkinsky, Kristina Eriksson, Carl-Fredrik Flach, Annie George-Chandy, Ali M Harandi, Michael Lebens, T. Lehner, Marianne Lindblad, Erik Nygren, Sukanya Raghavan, Joaquin Sanchez, M. Stanford, Jia-Bin Sun, Ann-Mari Svennerholm, Sara Tengvall
Immunol Lett - 2005-01-01 -
Cholera toxin induces a transient depletion of CD8+ intraepithelial lymphocytes in the rat small intestine as detected by microarray and
immunohistochemistry.
Carl-Fredrik Flach, Stefan Lange, Eva Jennische, Ivar Lönnroth, Jan Holmgren
Infection and immunity - 2005-01-01 -
Microarray analyses of the small intestinal mucosa during experimental and clinical
cholera
Carl-Fredrik Flach
- 2005-01-01 -
Cholera toxin induces expression of ion channels and carriers in rat small intestinal
mucosa.
Carl-Fredrik Flach, Stefan Lange, Eva Jennische, Ivar Lönnroth
FEBS letters - 2004-01-01