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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Phytophthora infestans small phospholipase D-like proteins elicit plant cell death and promote virulence
Meijer, Harold J.G. ; Schoina, Charikleia ; Wang, Shutong ; Bouwmeester, Klaas ; Hua, Chenlei ; Govers, Francine - \ 2018
Molecular Plant Pathology (2018). - ISSN 1464-6722
calcium - late blight disease - oomycete - phospholipases - phospholipids - signal peptide

The successful invasion of host tissue by (hemi-)biotrophic plant pathogens is dependent on modifications of the host plasma membrane to facilitate the two-way transfer of proteins and other compounds. Haustorium formation and the establishment of extrahaustorial membranes are probably dependent on a variety of enzymes that modify membranes in a coordinated fashion. Phospholipases, enzymes that hydrolyse phospholipids, have been implicated as virulence factors in several pathogens. The oomycete Phytophthora infestans is a hemibiotrophic pathogen that causes potato late blight. It possesses different classes of phospholipase D (PLD) proteins, including small PLD-like proteins with and without signal peptide (sPLD-likes and PLD-likes, respectively). Here, we studied the role of sPLD-like-1, sPLD-like-12 and PLD-like-1 in the infection process. They are expressed in expanding lesions on potato leaves and during in vitro growth, with the highest transcript levels in germinating cysts. When expressed in planta in the presence of the silencing suppressor P19, all three elicited a local cell death response that was visible at the microscopic level as autofluorescence and strongly boosted in the presence of calcium. Moreover, inoculation of leaves expressing the small PLD-like genes resulted in increased lesion growth and greater numbers of sporangia, but this was abolished when mutated PLD-like genes were expressed with non-functional PLD catalytic motifs. These results show that the three small PLD-likes are catalytically active and suggest that their enzymatic activity is required for the promotion of virulence, possibly by executing membrane modifications to support the growth of P. infestans in the host.

Consumption of β-glucans to spice up T cell treatment of tumors : a review
Graaff, Priscilla de; Govers, Coen ; Wichers, Harry J. ; Debets, Reno - \ 2018
Expert Opinion in Biological Therapy 18 (2018)10. - ISSN 1471-2598 - p. 1023 - 1040.
Adoptive T cell therapy - innate immunity - pattern recognition receptors - β-glucans

Introduction: Adoptive T-cell treatments of solid cancers have evolved into a robust therapy with objective response rates surpassing those of standardized treatments. Unfortunately, only a limited fraction of patients shows durable responses, which is considered to be due to a T cell-suppressive tumor microenvironment (TME). Here we argue that naturally occurring β-glucans can enable reversion of such T cell suppression by engaging innate immune cells and enhancing numbers and function of lymphocyte effectors. Areas covered: This review summarizes timely reports with respect to absorption, trafficking and immune stimulatory effects of β-glucans, particularly in relation to innate immune cells. Furthermore, we list effects toward well-being and immune functions in healthy subjects as well as cancer patients treated with orally administered β-glucans, extended with effects of β-glucan treatments in mouse cancer models. Expert opinion: Beta-glucans, when present in food and following uptake in the proximal gut, stimulate immune cells present in gut-associated lymphoid tissue and initiate highly conserved pro-inflammatory pathways. When tested in mouse cancer models, β-glucans result in better control of tumor growth and shift the TME toward a T cell-sensitive environment. Along these lines, we advocate that intake of β-glucans provides an accessible and immune-potentiating adjuvant when combined with adoptive T-cell treatments of cancer.

GPCR-bigrams : Enigmatic signaling components in oomycetes
Hoogen, Johan van den; Govers, Francine - \ 2018
PLoS Pathogens 14 (2018)7. - ISSN 1553-7366
Dissecting cellular signaling in Phytophthora
Hoogen, Johan van den - \ 2018
University. Promotor(en): Francine Govers. - Wageningen : Wageningen University - ISBN 9789463438667 - 141
The G-protein γ subunit of Phytophthora infestans is involved in sporangial development
Hoogen, Johan van den; Verbeek-de Kruif, Natalie ; Govers, Francine - \ 2018
Fungal Genetics and Biology 116 (2018). - ISSN 1087-1845 - p. 73 - 82.
G-protein subunit - GPCR - Oomycetes - Phytophthora - Signaling

The oomycete Phytophthora infestans is a notorious plant pathogen with potato and tomato as its primary hosts. Previous research showed that the heterotrimeric G-protein subunits Gα and Gβ have a role in zoospore motility and virulence, and sporangial development, respectively. Here, we present analyses of the gene encoding a Gγ subunit in P. infestans, Pigpg1. The overall similarity of PiGPG1 with non-oomycete Gγ subunits is low, with only the most conserved amino acids maintained, but similarity with its homologs in other oomycetes is high. Pigpg1 is expressed in all life stages and shows a similar expression profile as the gene encoding the Gβ subunit, Pigpb1. To elucidate its function, transformants were generated in which Pigpg1 is silenced or overexpressed and their phenotypes were analyzed. Pigpg1-silenced lines produce less sporangia, which are malformed. Altogether, the results show that PiGPG1 is crucial for proper sporangia development and zoosporogenesis. PiGPG1 is a functional Gγ, and likely forms a dimer with PiGPB1 that mediates signaling.

Phytophthora infestans enzymes and their role in the interaction with its hosts
Schoina, Charikleia - \ 2018
University. Promotor(en): Francine Govers; Klaas Bouwmeester. - Wageningen : Wageningen University - ISBN 9789463432870 - 198
Feeding the 10 billion: sustainabele future proteins
Govers, Coen ; Wichers, Harry - \ 2018
Reduction of obesity and related diseases by targeted nutritional treatment
Henquet, M.G.L. ; Boer, V.C.J. de; Keijer, J. ; Wichers, H.J. ; Govers, C.C.F.M. ; Bastiaan-Net, S. ; Bergervoet, J.H.W. ; Griensven, L.J.L.D. van - \ 2018
With 2.3 billion overweight and 700 million obese adults worldwide in 2015 (WHO), obesity and consequently diabetes type II are among the biggest global health problems. Even though dietary and lifestyle changes may eventually reduce obesity for some individuals, new safe and more efficacious drugs are required for successful weight reduction and treatment of type 2 diabetes in a large proportion of obese individuals. It has been shown that various G-protein coupled receptors (GPCRs) expressed in various tissues such as liver, muscle, pancreatic islets, immune cells and the central nervous system are involved. GPCRs are important targets for food components. The members of this large family of membrane proteins are involved in virtually every physiological process. This study will focus on the interaction between food ligands and GPCRs.
Genome-wide characterization of Phytophthora infestans metabolism : a systems biology approach
Rodenburg, Y.A. ; Seidl, M.F. ; Ridder, D. de; Govers, F. - \ 2018
Molecular Plant Pathology 19 (2018)6. - ISSN 1464-6722 - p. 1403 - 1413.
Genome-scale metabolic models (GEMs) provide a functional view of the complex network of biochemical reactions in the living cell. Initially mainly applied to reconstruct the metabolism of model organisms, the availability of increasingly sophisticated reconstruction methods and more extensive biochemical databases now make it possible to reconstruct GEMs for less well-characterized organisms, and have the potential to unravel the
metabolism in pathogen–host systems. Here, we present a GEM for the oomycete plant pathogen Phytophthora infestans as a first step towards an integrative model with its host. We predict the biochemical reactions in different cellular compartments and investigate the gene–protein–reaction associations in this model to obtain an impression of the biochemical capabilities of
P. infestans . Furthermore, we generate life stage-specific models to place the transcriptomic changes of the genes encoding metabolic enzymes into a functional context. In sporangia and zoospores, there is an overall down-regulation, most strikingly reflected in the fatty acid biosynthesis pathway. To investigate the robustness of the GEM, we simulate gene deletions to predict which enzymes are essential for in vitro growth. This model is an
essential first step towards an understanding of P. infestans and its interactions with plants as a system, which will help to formulate new hypotheses on infection mechanisms and disease prevention.
The ancient link between G-protein-coupled receptors and C-terminal phospholipid kinase domains
Hoogen, D.J. van den; Meijer, Harold J.G. ; Seidl, Michael F. ; Govers, Francine - \ 2018
MBio 9 (2018)1. - ISSN 2161-2129
Cell signaling - G-protein-coupled receptors - Oomycetes - Phospholipid-mediated signaling - Phytophthora
Sensing external signals and transducing these into intracellular responses requires a molecular signaling system that is crucial for every living organism. Two important eukaryotic signal transduction pathways that are often interlinked are G-protein signaling and phospholipid signaling. Heterotrimeric G-protein subunits activated by G-protein-coupled receptors (GPCRs) are typical stimulators of phospholipid signaling enzymes such as phosphatidylinositol phosphate kinases (PIPKs) or phospholipase C (PLC). However, a direct connection between the two pathways likely exists in oomycetes and slime molds, as they possess a unique class of GPCRs that have a PIPK as an accessory domain. In principle, these so-called GPCR-PIPKs have the capacity of perceiving an external signal (via the GPCR domain) that, via PIPK, directly activates downstream phospholipid signaling. Here we reveal the sporadic occurrence of GPCR-PIPKs in all eukaryotic supergroups, except for plants. Notably, all species having GPCR-PIPKs are unicellular microorganisms that favor aquatic environments. Phylogenetic analysis revealed that GPCR-PIPKs are likely ancestral to eukaryotes and significantly expanded in the last common ancestor of oomycetes. In addition to GPCR-PIPKs, we identified five hitherto-unknown classes of GPCRs with accessory domains, four of which are universal players in signal transduction. Similarly to GPCR-PIPKs, this enables a direct coupling between extracellular sensing and downstream signaling. Overall, our findings point to an ancestral signaling system in eukaryotes where GPCR-mediated sensing is directly linked to downstream responses. IMPORTANCE G-protein-coupled receptors (GPCRs) are central sensors that activate eukaryotic signaling and are the primary targets of human drugs. In this report, we provide evidence for the widespread though limited presence of a novel class of GPCRs in a variety of unicellular eukaryotes. These include free-living organisms and organisms that are pathogenic for plants, animals, and humans. The novel GPCRs have a C-terminal phospholipid kinase domain, pointing to a direct link between sensing external signals via GPCRs and downstream intracellular phospholipid signaling. Genes encoding these receptors were likely present in the last common eukaryotic ancestor and were lost during the evolution of higher eukaryotes. We further describe five other types of GPCRs with a catalytic accessory domain, the so-called GPCR-bigrams, four of which may potentially have a role in signaling. These findings shed new light onto signal transduction in microorganisms and provide evidence for alternative eukaryotic signaling pathways.
The Effect of Tomatine on Gene Expression and Cell Monolayer Integrity in Caco-2
Arena, Mattia ; Govers, C.C.F.M. ; Lotti, Concetta ; Ricciardi, Luigi ; Wichers, H.J. ; Mes, J.J. - \ 2018
Molecules 23 (2018)3. - ISSN 1420-3049
More understanding of the risk-benefit effect of the glycoalkaloid tomatine is required to be able to estimate the role it might play in our diet. In this work, we focused on effects towards intestinal epithelial cells based on a Caco-2 model in order to analyze the influence on the cell monolayer integrity and on the expression levels of genes involved in cholesterol/sterol biosynthesis (LDLR), lipid metabolism (NR2F2), glucose and amino acid uptake (SGLT1, PAT1), cell cycle (PCNA, CDKN1A), apoptosis (CASP-3, BMF, KLF6), tight junctions (CLDN4, OCLN2) and cytokine-mediated signaling (IL-8, IL1β, TSLP, TNF-α). Furthermore, since the bioactivity of the compound might vary in the presence of a food matrix and following digestion, the influence of both pure tomatine and in vitro digested tomatine with and without tomato fruit matrix was studied. The obtained results suggested that concentrations <20 µg/mL of tomatine, either undigested or in vitro digested, do not compromise the viability of Caco-2 cells and stimulate cytokine expression. This effect of tomatine, in vitro digested tomatine or in vitro digested tomatine with tomato matrix differs slightly, probably due to variations of bioactivity or bioavailability of the tomatine. The results lead to the hypothesis that tomatine acts as hormetic compound that can induce beneficial or risk toxic effects whether used in low or high dose.
RXLR effector diversity in Phytophthora infestans isolates determines recognition by potato resistance proteins; the case study AVR1 and R1
Du, Y. ; Weide, R. ; Zhao, Z. ; Msimuko, P. ; Govers, F. ; Bouwmeester, K. - \ 2018
Studies in Mycology 89 (2018). - ISSN 0166-0616 - p. 85 - 93.
Effector variation - Effector-triggered immunity (ETI) - Host defence - Late blight disease - Nucleotide-binding and leucine-rich repeat (NLR) protein - Potato resistance
Late blight disease caused by the plant pathogenic oomycete pathogen Phytophthora infestans is one of the most limiting factors in potato production. P. infestans is able to overcome introgressed late blight resistance by adaptation of effector genes. AVR1 is an RXLR effector that triggers immune responses when recognized by the potato resistance protein R1. P. infestans isolates avirulent on R1 plants were found to have AVR1 variants that are recognized by R1. Virulent isolates though, lack AVR1 but do contain a close homologue of AVR1, named A-L, of which all variants escape recognition by R1. Co-expression of AVR1 and R1 in Nicotiana benthamiana results in a hypersensitive response (HR). In contrast, HR is not activated when A-L is co-expressed with R1. AVR1 and A-L are highly similar in structure. They share two W motifs and one Y motif in the C-terminal part but differ in the T-region, a 38 amino acid extension at the carboxyl-terminal tail of AVR1 lacking in A-L. To pinpoint what determines R1-mediated recognition of AVR1 we tested elicitor activity of AVR1 and A-L chimeric and deletion constructs by co-expression with R1. The T-region is important as it enables R1-mediated recognition of A-L, not only when fused to A-L but also via trans-complementation. Yet, AVR1 lacking the T-region is still active as an elicitor of HR, but this activity is lost when certain motifs are swapped with A-L. These data show that A-L circumvents R1 recognition not only because it lacks the T-region, but also because of differences in the conserved C-terminal effector motifs.
Review of the health effects of berries and their phytochemicals on the digestive and immune systems
Govers, Coen ; Kasikci, Muzeyyen Berkel ; Sluis, Addie A. van der; Mes, Jurriaan J. - \ 2018
Nutrition Reviews 76 (2018)1. - ISSN 0029-6643 - p. 29 - 46.
Berry - Digestive system - Immune system - In vivo - Phytochemicals
Berries are generally considered beneficial to health. This health-promoting potential has mainly been ascribed to berries' phytochemical and vitamin content, and little attention has been paid to the potential benefits of berries for the digestive tract, despite this being the first point of contact. In vivo studies that described the health effects of berries on individual parts of the digestive tract (ie, the mouth, esophagus, stomach, small and large intestine, microbiome, and immune system) were reviewed. Immune effects were included because a large part of the immune system is located in the intestine. Beneficial health effects were mainly observed for whole berry extracts, not individual berry components. These effects ranged from support of the immune system and beneficial microbiota to reduction in the number and size of premalignant and malignant lesions. These results demonstrate the potency of berries and suggest berries can serve as a strong adjuvant to established treatments or therapies for a variety of gastrointestinal and immune-related illnesses.
Solanaceous exocyst subunits are involved in immunity to diverse plant pathogens
Du, Yu ; Overdijk, Elysa J.R. ; Berg, Jeroen A. ; Govers, Francine ; Bouwmeester, Klaas - \ 2018
Journal of Experimental Botany 69 (2018)3. - ISSN 0022-0957 - p. 655 - 666.
Basal defence - exocyst complex - exocytosis - gene silencing - phylogenetic analysis - plant resistance - Solanaceous plants - vesicle trafficking
The exocyst, a multiprotein complex consisting of eight subunits, plays an essential role in many biological processes by mediating secretion of post-Golgi-derived vesicles towards the plasma membrane. In recent years, roles for plant exocyst subunits in pathogen defence have been uncovered, largely based on studies in the model plant Arabidopsis. Only a few studies have been undertaken to assign the role of exocyst subunits in plant defence in other plants species, including crops. In this study, predicted protein sequences from exocyst subunits were retrieved by mining databases from the Solanaceous plants Nicotiana benthamiana, tomato, and potato. Subsequently, their evolutionary relationship with Arabidopsis exocyst subunits was analysed. Gene silencing in N. benthamiana showed that several exocyst subunits are required for proper plant defence against the (hemi-)biotrophic plant pathogens Phytophthora infestans and Pseudomonas syringae. In contrast, some exocyst subunits seem to act as susceptibility factors for the necrotrophic pathogen Botrytis cinerea. Furthermore, the majority of the exocyst subunits were found to be involved in callose deposition, suggesting that they play a role in basal plant defence. This study provides insight into the evolution of exocyst subunits in Solanaceous plants and is the first to show their role in immunity against multiple unrelated pathogens.
Seagrass leaf element content : A global overview
Vonk, J.A. ; Smulders, Fee O.H. ; Christianen, Marjolijn J.A. ; Govers, Laura L. - \ 2018
Marine Pollution Bulletin 134 (2018). - ISSN 0025-326X - p. 123 - 133.
Environmental adaptation - Evolutionary history - Micronutrients - Plant physiology - Seagrass - Successional stage
Knowledge on the role of seagrass leaf elements and in particular micronutrients and their ranges is limited. We present a global database, consisting of 1126 unique leaf values for ten elements, obtained from literature and unpublished data, spanning 25 different seagrass species from 28 countries. The overall order of average element values in seagrass leaves was Na. >. K. >. Ca. >. Mg. >. S. >. Fe. >. Al. >. Si. >. Mn. >. Zn. Although we observed differences in leaf element content between seagrass families, high intraspecific variation indicated that leaf element content was more strongly determined by environmental factors than by evolutionary history. Early successional species had high leaf Al and Fe content. In addition, seagrass leaf element content also showed correlations with macronutrients (N and P), indicating that productivity also depends on other elements. Expected genomes of additional seagrass species in combination with experiments manipulating (micro)nutrients and environmental drivers might enable us to unravel the importance of various elements to sustain productive and flourishing meadows.
Food-Derived β-glucans: Polarization towards M1-like macrophages
Graaff, Priscilla de; Laar, Amar van; Tomassen, M.M.M. ; Berrevoets, C. ; Debets, R. ; Govers, C.C.F.M. - \ 2017
Effectievere afweer tegen kanker met voedingsvezels?
Govers, Coen - \ 2017

Onderzoeker van de week: Coen Govers

Bomen en plantenverdelgers
Govers, F. - \ 2017
In: Schimmels Stichting Biowetenschappen en Maatschappij (Cahier Biowetenschappen en Maatschappij 4) - ISBN 9789073196889 - p. 29 - 32.
Een plaag voor de landbouw
Govers, F. - \ 2017
In: Schimmels Stichting Biowetenschappen en Maatschappij (Cahier Biowetenschappen en Maatschappij 4) - ISBN 9789073196889 - p. 50 - 55.
Water-soluble polysaccharide extracts from the oyster culinary-medicinal mushroom pleurotus ostreatus (Agaricomycetes) with HMGCR inhibitory activity
Gil-Ramírez, Alicia ; Smiderle, Fhernanda R. ; Morales, Diego ; Govers, Coen ; Synytsya, Andriy ; Wichers, Harry J. ; Iacomini, Marcello ; Soler-Rivas, Cristina - \ 2017
International Journal of Medicinal Mushrooms 19 (2017)10. - ISSN 1521-9437 - p. 879 - 892.
Caco2 - Cholesterol - HMGCR - Medicinal mushrooms - Pleurotus ostreatus - Polysaccharides - β-glucans
Water extracts from Pleurotus ostreatus containing no statins showed 3-hydroxy-3-methyl-glutaryl CoA reductase (HMGCR) inhibitory activity (in vitro) that might be due to specific water-soluble polysaccharides (WSPs); when isolated and deproteinized, increasing concentrations of the WSP extract induced higher inhibition. The WSP extract contained mainly β-glucans, mannogalactans, and glycogen (e.g., α-glucans), although derivatives or fragments with lower molecular weights (between 14 and 3.5 kDa) were present and were able to induce the inhibitory activity. The extract contained more β-(1→3)-glucans than β-(1→3),(1→6)-glucans, and they partially survived digestion and managed to pass through Caco2 cell monolayers to the lower compartment after in vitro digestion and transport experiments. The WSP might also modulate Caco2 membrane integrity.
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