Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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    Guide-free Cas9 from pathogenic Campylobacter jejuni bacteria causes severe damage to DNA
    Saha, Chinmoy ; Mohanraju, Prarthana ; Stubbs, Andrew ; Dugar, Gaurav ; Hoogstrate, Youri ; Kremers, Gert Jan ; Cappellen, Wiggert A. Van; Horst-Kreft, Deborah ; Laffeber, Charlie ; Lebbink, Joyce H.G. ; Bruens, Serena ; Gaskin, Duncan ; Beerens, Dior ; Klunder, Maarten ; Joosten, Rob ; Demmers, Jeroen A.A. ; Gent, Dik Van; Mouton, Johan W. ; Spek, Peter J. Van Der; Oost, John Van Der; Baarlen, Peter Van; Louwen, Rogier - \ 2020
    Science Advances 6 (2020)25. - ISSN 2375-2548

    CRISPR-Cas9 systems are enriched in human pathogenic bacteria and have been linked to cytotoxicity by an unknown mechanism. Here, we show that upon infection of human cells, Campylobacter jejuni secretes its Cas9 (CjeCas9) nuclease into their cytoplasm. Next, a native nuclear localization signal enables CjeCas9 nuclear entry, where it catalyzes metal-dependent nonspecific DNA cleavage leading to cell death. Compared to CjeCas9, native Cas9 of Streptococcus pyogenes (SpyCas9) is more suitable for guide-dependent editing. However, in human cells, native SpyCas9 may still cause some DNA damage, most likely because of its ssDNA cleavage activity. This side effect can be completely prevented by saturation of SpyCas9 with an appropriate guide RNA, which is only partially effective for CjeCas9. We conclude that CjeCas9 plays an active role in attacking human cells rather than in viral defense. Moreover, these unique catalytic features may therefore make CjeCas9 less suitable for genome editing applications.

    Dutch-Indonesian programme on Food Security in the livestock sector (DIFS-live): poultry meat : Results of the poultry meat programme 2014-2018; main report
    Horne, Peter van; Emous, Rick van; Joosten, Frank ; Tacken, Gemma ; Leenstra, Ferry - \ 2020
    Wageningen : Wageningen Livestock Research (Rapport / Wageningen Livestock Research 1259) - 60
    In this report, the design and results of the poultry meat program in the Dutch Indonesian Food Safety Program (DIFSlive) are presented. The program consisted of a consumer campaign to promote trade in and consumption of chilled poultry meat, scenario studies into the development of poultry meat production, improvements in small-scale slaughtering and cooling of poultry and improvements in broiler farming.
    Correction to: Rewiring of glucose metabolism defines trained immunity induced by oxidized low-density lipoprotein
    Keating, Samuel T. ; Groh, Laszlo ; Thiem, Kathrin ; Bekkering, Siroon ; Li, Yang ; Matzaraki, Vasiliki ; Heijden, Charlotte D.C.C. van der; Puffelen, Jelmer H. van; Lachmandas, Ekta ; Jansen, Trees ; Oosting, Marije ; Bree, L.C.J. de; Koeken, Valerie A.C.M. ; Moorlag, Simone J.C.F.M. ; Mourits, Vera P. ; Diepen, Janna van; Stienstra, Rinke ; Novakovic, Boris ; Stunnenberg, Hendrik G. ; Crevel, Reinout van; Joosten, Leo A.B. ; Netea, Mihai G. ; Riksen, Niels P. - \ 2020
    Journal of Molecular Medicine 98 (2020). - ISSN 0946-2716

    The correct name of the 17th Author is presented in this paper. In the paragraph “Metabolic analysis” of the Method section “an XFp Analyzer” should be changed to “an XFe96 Analyzer”.

    Rewiring of glucose metabolism defines trained immunity induced by oxidized low-density lipoprotein
    Keating, Samuel T. ; Groh, Laszlo ; Thiem, Kathrin ; Bekkering, Siroon ; Li, Yang ; Matzaraki, Vasiliki ; Heijden, Charlotte D.C.C. van der; Puffelen, Jelmer H. van; Lachmandas, Ekta ; Jansen, Trees ; Oosting, Marije ; Bree, L.C.J. de; Koeken, Valerie A.C.M. ; Moorlag, Simone J.C.F.M. ; Mourits, Vera P. ; Diepen, Janna van; Stienstra, Rinke ; Novakovic, Boris ; Stunnenberg, Hendrik G. ; Crevel, Reinout van; Joosten, Leo A.B. ; Netea, Mihai G. ; Riksen, Niels P. - \ 2020
    Journal of Molecular Medicine 98 (2020). - ISSN 0946-2716 - p. 819 - 831.
    Atherosclerosis - Cardiovascular disease - Diabetes complications - Glycolysis - Immunometabolism - Inflammation - Trained immunity

    Abstract: Stimulation of monocytes with microbial and non-microbial products, including oxidized low-density lipoprotein (oxLDL), induces a protracted pro-inflammatory, atherogenic phenotype sustained by metabolic and epigenetic reprogramming via a process called trained immunity. We investigated the intracellular metabolic mechanisms driving oxLDL-induced trained immunity in human primary monocytes and observed concomitant upregulation of glycolytic activity and oxygen consumption. In two separate cohorts of healthy volunteers, we assessed the impact of genetic variation in glycolytic genes on the training capacity of monocytes and found that variants mapped to glycolytic enzymes PFKFB3 and PFKP influenced trained immunity by oxLDL. Subsequent functional validation with inhibitors of glycolytic metabolism revealed dose-dependent inhibition of trained immunity in vitro. Furthermore, in vivo administration of the glucose metabolism modulator metformin abrogated the ability for human monocytes to mount a trained response to oxLDL. These findings underscore the importance of cellular metabolism for oxLDL-induced trained immunity and highlight potential immunomodulatory strategies for clinical management of atherosclerosis. Key messages: Brief stimulation of monocytes to oxLDL induces a prolonged inflammatory phenotype.This is due to upregulation of glycolytic metabolism.Genetic variation in glycolytic genes modulates oxLDL-induced trained immunity.Pharmacological inhibition of glycolysis prevents trained immunity.

    Review of insect pathogen risks for the black soldier fly (Hermetia illucens) and guidelines for reliable production
    Joosten, Lotte ; Lecocq, Antoine ; Jensen, Annette Bruun ; Haenen, Olga ; Schmitt, Eric ; Eilenberg, Jørgen - \ 2020
    Entomologia Experimentalis et Applicata 168 (2020)6-7. - ISSN 0013-8703 - p. 432 - 447.
    bacteria - biocontrol agents - black soldier fly - Diptera - entomopathogens - epidemiology - feed and food - fungi - guidelines - Hermetia illuscens - immune system - protozoa - Stratiomyidae - viruses

    Black soldier fly [BSF; Hermetia illucens L. (Diptera: Stratiomyidae)] larvae are very effective in transforming low-grade food waste into valuable high-end proteins and fat, in intensive production facilities. The production output of this species is growing quickly, but upscaling brings risks to the health status of the reared insects. Until now, not a single major case of disease outbreak caused by a pathogen in a BSF production unit has been reported. This contrasts with data on other species of mass-produced insects, which have experienced various disease outbreaks, indicating that BSFs are comparatively resistant to insect diseases. Further, there are no records of natural infections caused by entomopathogens in BSF. In this review, the known entomopathogens of Diptera, especially BSF, and their potential risks for causing disease in these insects are summarized.

    Antimicrobial resistance prevalence in commensal Escherichia coli from broilers, fattening turkeys, fattening pigs and veal calves in European countries and association with antimicrobial usage at country level
    Ceccarelli, Daniela ; Hesp, Ayla ; Goot, Jeanet Van Der; Joosten, Philip ; Sarrazin, Steven ; Wagenaar, Jaap A. ; Dewulf, Jeroen ; Mevius, Dik J. - \ 2020
    Journal of Medical Microbiology 69 (2020)4. - ISSN 0022-2615 - p. 537 - 547.
    antimicrobial resistance - antimicrobial usage - Escherichia coli - Europe - livestock. - MIC

    The aim of this article is to report on antimicrobial resistance (AMR) in commensal Escherichia coli from livestock from several European countries. The relationships with antimicrobial usage (AMU) at country level and harmonized indicators to cover the most relevant AMR aspects for human health in animal production were also investigated. E. coli were isolated in faeces from broilers and fattening pigs (from nine countries), and fattening turkeys and veal calves (from three countries) and screened against a fixed antimicrobial panel. AMU data were collected at farm and average treatment incidences stratified by antimicrobial class, country and livestock species were calculated. Associations between AMR and AMU at country level were analysed. Independent of animal species, the highest resistance was observed for ampicillin, sulphamethoxazole, tetracycline and trimethoprim. E. coli from broilers showed the highest resistance level for (fluoro)quinolones, and multidrug resistance peaked in broilers and fattening turkeys. Colistin resistance was observed at very low levels with the exception of fattening turkeys. High resistance to third-and fourth-generation cephalosporins was detected in broilers and fattening turkeys. The lowest levels of resistance were for meropenem, azithromycin and tigecycline (1 %). Significant correlations between resistance and usage at country level were detected in broilers for polymyxins and aminoglycosides, and in fattening pigs for cephalosporins, amphenicols, fluoroquinolones and polymyxins. None of the correlations observed between AMR and AMU were statistically significant for fattening turkey and veal calves. The strength of the analysis performed here is the correlation of aggregated data from the same farms at country level for both AMU and AMR within antimicrobial classes.

    A satellite repeat-derived piRNA controls embryonic development of Aedes
    Halbach, Rebecca ; Miesen, Pascal ; Joosten, Joep ; Taşköprü, Ezgi ; Rondeel, Inge ; Pennings, Bas ; Vogels, Chantal B.F. ; Merkling, Sarah H. ; Koenraadt, Constantianus J. ; Lambrechts, Louis ; Rij, Ronald P. van - \ 2020
    Nature 580 (2020)7802. - ISSN 0028-0836 - p. 274 - 277.

    Tandem repeat elements such as the diverse class of satellite repeats occupy large parts of eukaryotic chromosomes, mostly at centromeric, pericentromeric, telomeric and subtelomeric regions1. However, some elements are located in euchromatic regions throughout the genome and have been hypothesized to regulate gene expression in cis by modulating local chromatin structure, or in trans via transcripts derived from the repeats2–4. Here we show that a satellite repeat in the mosquito Aedes aegypti promotes sequence-specific gene silencing via the expression of two PIWI-interacting RNAs (piRNAs). Whereas satellite repeats and piRNA sequences generally evolve extremely quickly5–7, this locus was conserved for approximately 200 million years, suggesting that it has a central function in mosquito biology. piRNA production commenced shortly after egg laying, and inactivation of the more abundant piRNA resulted in failure to degrade maternally deposited transcripts in the zygote and developmental arrest. Our results reveal a mechanism by which satellite repeats regulate global gene expression in trans via piRNA-mediated gene silencing that is essential for embryonic development.

    Antimicrobial usage and resistance in companion animals: A cross-sectional study in three european countries
    Joosten, Philip ; Ceccarelli, Daniela ; Odent, Evelien ; Sarrazin, Steven ; Graveland, Haitske ; Gompel, Liese Van; Battisti, Antonio ; Caprioli, Andrea ; Franco, Alessia ; Wagenaar, Jaap A. ; Mevius, Dik ; Dewulf, Jeroen - \ 2020
    Antibiotics 9 (2020)2. - ISSN 2079-6382
    Antimicrobial resistance - Antimicrobial use - Colistin resistance - Companion animals - Critically important antimicrobials - One health

    Companion animals have been described as potential reservoirs of antimicrobial resistance (AMR), however data remain scarce. Therefore, the objectives were to describe antimicrobial usage (AMU) in dogs and cats in three European countries (Belgium, Italy, and The Netherlands) and to investigate phenotypic AMR. A questionnaire and one fecal sample per animal (n = 303) were collected over one year and AMU was quantified using treatment incidence (TI). Phenotypic resistance profiles of 282 Escherichia coli isolates were determined. Nineteen percent of the animals received at least one antimicrobial treatment six months preceding sampling. On average, cats and dogs were treated with a standard daily dose of antimicrobials for 1.8 and 3.3 days over one year, respectively. The most frequently used antimicrobial was amoxicillin-clavulanate (27%). Broad-spectrum antimicrobials and critically important antimicrobials for human medicine represented 83% and 71% of the total number of treatments, respectively. Resistance of E. coli to at least one antimicrobial agent was found in 27% of the isolates. The most common resistance was to ampicillin (18%). Thirteen percent was identified as multidrug resistant isolates. No association between AMU and AMR was found in the investigated samples. The issue to address, regarding AMU in companion animal, lies within the quality of use, not the quantity. Especially from a One-Health perspective, companion animals might be a source of transmission of resistance genes and/or resistant bacteria to humans.

    Mice Deficient in the IL-1β Activation Genes Prtn3, Elane, and Casp1 Are Protected Against the Development of Obesity-Induced NAFLD
    Mirea, Andreea Manuela ; Stienstra, Rinke ; Kanneganti, Thirumala Devi ; Tack, Cees J. ; Chavakis, Triantafyllos ; Toonen, Erik J.M. ; Joosten, Leo A.B. - \ 2020
    Inflammation Research 43 (2020). - ISSN 0360-3997 - p. 1054 - 1064.
    IL-1 beta - inflammation - neutrophil serine proteases - obesity

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Inflammatory pathways contribute to disease pathogenesis; however, regulation of the underlying mechanism is not completely understood. IL-1β, a pro-inflammatory cytokine, participates in the development and progression of NAFLD. To become bioactive, IL-1β requires enzymatic processing. Mechanisms that activate IL-1β include the classical NLRP3 inflammasome-caspase-1 and the neutrophil serine proteases, neutrophil elastase, and proteinase-3. Several studies have shown that both caspase-1 and the neutrophil serine proteases are important for NAFLD development. However, it is unknown whether these pathways interact and if they have a synergistic effect in promoting NAFLD. In the present study, we developed a novel and unique mouse model by intercrossing caspase-1/11 knockout mice with neutrophil elastase/proteinase-3 double knockout mice. Subsequently, these mice were examined regarding the development of high-fat diet–induced NAFLD. Our results show that mice deficient in caspase-1, neutrophil elastase, and proteinase-3 were protected from developing diet-induced weigh gain, liver steatosis, and adipose tissue inflammation when compared with controls. We conclude that pathways that process pro-IL-1β to bioactive IL-1β play an important role in promoting the development of NAFLD and obesity-induced inflammation. Targeting these pathways could have a therapeutic potential in patients with NAFLD.

    Regulation and activation of SOBIR1-containing receptor complexes involved in plant immune signalling
    Wu, Jinbin - \ 2020
    Wageningen University. Promotor(en): B.P.H.J. Thomma, co-promotor(en): M.H.A.J. Joosten. - Wageningen : Wageningen University - ISBN 9789463951821 - 183

    The tomato cell surface receptor-like protein (RLP) Cf-4 confers resistance to Avr4-secreting strains of the fungus Cladosporium fulvum, which causes tomato leaf mould disease. Cf-4 constitutively interacts with the receptor-like kinase (RLK) SOBIR1 and interacts with the RLK BAK1 upon recognition of Avr4 by Cf-4. Formation of the Cf-4/SOBIR1/BAK1 complex is proposed to trigger phosphorylation of the intracellular kinase domains of SOBIR1 and BAK1, which subsequently activate downstream signalling resulting in plant immunity. However, components involved in regulating the Avr4-induced formation and subsequent activation of the Cf-4/SOBIR1/BAK1 complex remain unknown. In addition, downstream components required for Cf-4 signalling are largely unknown. The work described in this thesis is aimed at gaining more insight into the molecular mechanisms of Cf-4 signalling. Furthermore, the application of the gained knowledge to genetically engineer plant immunity is pursued. Additionally, as SOBIR1, which is functionally required for all RLPs mediating immunity, also interacts with the RLP CLAVATA2 (CLV2) involved in development, the significance of the CLV2/SOBIR1 complex is investigated.

    Van Proeftuin Veenweiden naar Klimaatslim Boeren op Veen : rapportage
    Joosten, Leo ; Migchels, Gerard ; Leeuwen, Marieke van - \ 2019
    Wageningen : Wageningen Livestock Research (Wageningen Livestock Research rapportage 1202) - 4
    Mogelijkheden tot vermarkten van reducties in ammoniakemissie in het westelijk veenweidegebied: rapportage
    Joosten, Leo ; Migchels, Gerard ; Leeuwen, Marieke van - \ 2019
    Wageningen : Wageningen Livestock Research (Wageningen Livestock Research rapportage 1203) - 13
    Naar een ketengerichte aanpak om ammoniakemissie te reduceren : Ontwerp en toepassing
    Migchels, Gerard ; Joosten, Leo ; Leeuwen, Marieke van - \ 2019
    Wageningen : Wageningen Livestock Research (Rapport / Wageningen Livestock Research 1197) - 31
    Naar een integraal gebiedsgerichte aanpak om ammoniakemissie te reduceren : Ontwerp en pilot
    Leeuwen, Marieke van; Migchels, Gerard ; Joosten, Leo - \ 2019
    Wageningen : Wageningen Livestock Research (Rapport / Wageningen Livestock Research 1198) - 28
    Naar een depositiegerichte aanpak van ammoniakemissies rond de Nieuwkoopse Plassen : Scenariostudie voor Proeftuin Veenweiden
    Joosten, Leo ; Verhoeff, Teus ; Wilmot, Mark ; Migchels, Gerard ; Dijk, Cathy - \ 2019
    Wageningen : Wageningen Livestock Research (Rapport / Wageningen Livestock Research 1199) - 28
    Borgen van maatregelen om ammoniakemissie te reduceren
    Migchels, Gerard ; Joosten, Leo ; Leeuwen, Marieke van; Ferwerda, Reina ; Wim Houwers, Wim - \ 2019
    Wageningen : Wageningen Livestock Research (Rapport / Wageningen Livestock Research 1196) - 42
    Eerste verkenning arrangementen om ammoniakemissie in het westelijke veenweidegebied te reduceren
    Migchels, Gerard ; Leeuwen, Marieke van; Joosten, Leo - \ 2019
    Wageningen : Wageningen Livestock Research (Rapport / Wageningen Livestock Research 1195) - 17
    Associations between antimicrobial use and the faecal resistome on broiler farms from nine European countries
    Luiken, Roosmarijn E.C. ; Gompel, Liese Van; Munk, Patrick ; Sarrazin, Steven ; Joosten, Philip ; Dorado-García, Alejandro ; Borup Hansen, Rasmus ; Knudsen, Berith E. ; Bossers, Alex ; Wagenaar, Jaap A. ; Aarestrup, Frank M. ; Dewulf, Jeroen ; Mevius, Dik J. ; Heederik, Dick J.J. ; Smit, Lidwien A.M. ; Schmitt, Heike - \ 2019
    Journal of Antimicrobial Chemotherapy 74 (2019)9. - ISSN 0305-7453 - p. 2596 - 2604.

    OBJECTIVES: To determine associations between farm- and flock-level antimicrobial usage (AMU), farm biosecurity status and the abundance of faecal antimicrobial resistance genes (ARGs) on broiler farms. METHODS: In the cross-sectional pan-European EFFORT study, conventional broiler farms were visited and faeces, AMU information and biosecurity records were collected. The resistomes of pooled faecal samples were determined by metagenomic analysis for 176 farms. A meta-analysis approach was used to relate total and class-specific ARGs (expressed as fragments per kb reference per million bacterial fragments, FPKM) to AMU (treatment incidence per DDD, TIDDDvet) per country and subsequently across all countries. In a similar way, the association between biosecurity status (Biocheck.UGent) and the resistome was explored. RESULTS: Sixty-six (38%) flocks did not report group treatments but showed a similar resistome composition and roughly similar ARG levels to antimicrobial-treated flocks. Nevertheless, we found significant positive associations between β-lactam, tetracycline, macrolide and lincosamide, trimethoprim and aminoglycoside antimicrobial flock treatments and ARG clusters conferring resistance to the same class. Similar associations were found with purchased products. In gene-level analysis for β-lactams and macrolides, lincosamides and streptogramins, a significant positive association was found with the most abundant gene clusters blaTEM and erm(B). Little evidence was found for associations with biosecurity. CONCLUSIONS: The faecal microbiome in European broilers contains a high diversity of ARGs, even in the absence of current antimicrobial selection pressure. Despite this, the relative abundance of genes and the composition of the resistome is positively related to AMU in European broiler farms for several antimicrobial classes.

    Plant Immunity: Thinking Outside and Inside the Box
    Burgh, Aranka M. van der; Joosten, Matthieu H.A.J. - \ 2019
    Trends in Plant Science 24 (2019)7. - ISSN 1360-1385 - p. 587 - 601.
    danger signal - effector-triggered immunity - extracellular immunogenic pattern - intracellular immunogenic pattern - pattern-triggered immunity - plant immunity - spatial immunity model

    Models are extensively used to describe the coevolution of plants and microbial attackers. Such models distinguish between different classes of plant immune responses, based on the type of danger signal that is recognized or on the strength of the defense response that the danger signal provokes. However, recent molecular and biochemical advances have shown that these dichotomies are blurred. With molecular proof in hand, we propose here to abandon the current classification of plant immune responses, and to define the different forms of plant immunity solely based on the site of microbe recognition – either extracellular or intracellular. Using this spatial partition, our ‘spatial immunity model’ facilitates a broadly inclusive, but clearly distinguishing nomenclature to describe immune signaling in plant–microbe interactions.

    Distant Non-Obvious Mutations Influence the Activity of a Hyperthermophilic Pyrococcusfuriosus Phosphoglucose Isomerase
    Subramanian, Kalyanasundaram ; Mitusińska, Karolina ; Raedts, John ; Almourfi, Feras ; Joosten, Henk Jan ; Hendriks, Sjon ; Sedelnikova, Svetlana E. ; Kengen, Servé W.M. ; Hagen, Wilfred R. ; Góra, Artur ; Martins Dos Santos, Vitor A.P. ; Baker, Patrick J. ; Oost, John van der; Schaap, Peter J. - \ 2019
    Biomolecules 9 (2019)6. - ISSN 2218-273X
    Comulator - cupin phosphoglucose isomerase - Protein engineering - Pyrococcus furiosus - solvent access

    The cupin-type phosphoglucose isomerase (PfPGI) from the hyperthermophilic archaeon Pyrococcus furiosus catalyzes the reversible isomerization of glucose-6-phosphate to fructose-6-phosphate. We investigated PfPGI using protein-engineering bioinformatics tools to select functionally-important residues based on correlated mutation analyses. A pair of amino acids in the periphery of PfPGI was found to be the dominant co-evolving mutation. The position of these selected residues was found to be non-obvious to conventional protein engineering methods. We designed a small smart library of variants by substituting the co-evolved pair and screened their biochemical activity, which revealed their functional relevance. Four mutants were further selected from the library for purification, measurement of their specific activity, crystal structure determination, and metal cofactor coordination analysis. Though the mutant structures and metal cofactor coordination were strikingly similar, variations in their activity correlated with their fine-tuned dynamics and solvent access regulation. Alternative, small smart libraries for enzyme optimization are suggested by our approach, which is able to identify non-obvious yet beneficial mutations.

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