Mark Zwart

Dr. Mark Zwart

Researcher | Tenure Track

Bezoekadres

Droevendaalsesteeg 10
6708 PB Wageningen

+31 (0) 317 47 34 00

The Netherlands

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From zero to hero? Whereas a few viruses cause major problems for human health, most don't infect people and are integral parts of nature. So what viruses do we find in the wild, and how do they impact ecosystems? That's what my team and I are exploring.

Biografie

During my undergraduate degree, one of my mentors discouraged me from working on viruses because "we know everything about them". After all, we had more complete genome sequences than for any other organism and many insights in molecular biology are closely linked to viruses. What more could there be to learn about these simple life forms with relatively few genes? It turns out science was just beginning to scratch the surface! Nowadays we know that viruses are abundant in all environments, that they can have complex interactions with their host organisms despite their small sizes, and that they can impact whole ecosystems in many different ways. I have worked on the evolutionary biology, genetics and ecology of a number of different viruses, focusing on the plant viruses in recent years. I was initially interested in understanding the kinetics of virus infection and the evolution of major changes in their genomes. Now the focus of my work is on understanding how virus genome structure is linked to ecology and evolution, describing virus biodiversity in plant communities from natural ecosystems, and understanding how virus communities affect the composition and functioning of ecosystems. My dream is that we can predict patterns of virus spread and evolution in natural systems, and in doing so leverage these intriguing life forms.

CV

Publicaties

Peer-reviewed publicaties

  • New Phytologist
    2022

    Plant neighbours can make or break the disease transmission chain of a fungal root pathogen

    Eline Ampt, Jasper van Ruijven, Mark Zwart, Jos M. Raaijmakers, Aad J Termorshuizen, Liesje Mommer
    Biodiversity can reduce or increase disease transmission. These divergent effects suggest that community composition rather than diversity per se determines disease transmission. In natural plant communities, little is known about the functional roles of neighbouring plant species in belowground disease transmission.
    Here, we experimentally investigated disease transmission of a fungal root pathogen (Rhizoctonia solani) in two focal plant species in combinations with four neighbour species of two ages. We developed stochastic models to test the relative importance of two transmission-modifying mechanisms: (1) infected hosts serve as nutrient supply to increase hyphal growth, so that successful disease transmission is self-reinforcing; and (2) plant resistance increases during plant development.
    Neighbouring plants either reduced or increased disease transmission in the focal plants. These effects depended on neighbour age, but could not be explained by a simple dichotomy between hosts and nonhost neighbours. Model selection revealed that both transmission-modifying mechanisms are relevant and that focal host–neighbour interactions changed which mechanisms steered disease transmission rate.
    Our work shows that neighbour-induced shifts in the importance of these mechanisms across root networks either make or break disease transmission chains. Understanding how diversity affects disease transmission thus requires integrating interactions between focal and neighbour species and their pathogens.
    https://doi.org/10.1111/nph.17866
  • Journal of Theoretical Biology
    2022

    Second compartment widens plasmid invasion conditions

    Jesse B. Alderliesten, Mark Zwart, J. Arjan G. M. de Visser, Arjan Stegeman, Egil A. J. Fischer

    Understanding under which conditions conjugative plasmids encoding antibiotic resistance can invade bacterial communities in the gut is of particular interest to combat the spread of antibiotic resistance within and between animals and humans. We extended a one-compartment model of conjugation to a two-compartment model, to analyse how differences in plasmid dynamics in the gut lumen and at the gut wall affect the invasion of plasmids. We compared scenarios with one and two compartments, different migration rates between the lumen and wall compartments, and different population dynamics. We focused on the effect of attachment and detachment rates on plasmid dynamics, explicitly describing pair formation followed by plasmid transfer in the pairs. The parameter space allowing plasmid invasion in the one-compartment model is affected by plasmid costs and intrinsic conjugation rates of the transconjugant, but not by these characteristics of the donor. The parameter space allowing plasmid invasion in the two-compartment model is affected by attachment and detachment rates in the lumen and wall compartment, and by the bacterial density at the wall. The one- and two-compartment models predict the same parameter space for plasmid invasion if the conditions in both compartments are equal to the conditions in the one-compartment model. In contrast, the addition of the wall compartment widens the parameter space allowing invasion compared with the one-compartment model, if the density at the wall is higher than in the lumen, or if the attachment rate at the wall is high and the detachment rate at the wall is low. We also compared the pair-formation models with bulk-conjugation models that describe conjugation by instantaneous transfer of the plasmid at contact between cells, without explicitly describing pair formation. Our results show that pair-formation and bulk-conjugation models predict the same parameter space for plasmid invasion. From our simulations, we conclude that conditions at the gut wall should be taken into account to describe plasmid dynamics in the gut and that transconjugant characteristics rather than donor characteristics should be used to parameterize the models.

    https://doi.org/10.1016/j.jtbi.2021.110937
  • Frontiers in Virology
    29-04-2021

    Five Challenges in the Field of Viral Diversity and Evolution

    Rafael Sanjuán, Christopher J.R. Illingworth, Jemma L. Geoghegan, Jaime Iranzo, Mark Zwart, Alexander T. Ciota, Gonzalo Moratorio, Selma Gago-Zachert, Siobain Duffy, Dhanasekaran Vijaykrishna
    Viral diversity and evolution play a central role in processes such as disease emergence, vaccine failure, drug resistance, and virulence. However, significant challenges remain to better understand and manage these processes. Here, we discuss five of these challenges. These include improving our ability to predict viral evolution, developing more relevant experimental evolutionary systems, integrating viral dynamics and evolution at different scales, systematic appraisal of the virosphere, and deepening our understanding of virus-virus interactions. Intensifying future research on these areas should improve our ability to combat viral diseases, as well as to exploit viral diversity and evolution for biotechnological purposes.
    https://doi.org/10.3389/fviro.2021.684949
  • Virus Evolution
    2021

    Unresolved advantages of multipartitism in spatially structured environments

    Mark Zwart, Stéphane Blanc, Marcelle Johnson, Susanna Manrubia, Yannis Michalakis, Mircea T. Sofonea

    Multipartite viruses have segmented genomes and package each of their genome segments individually into distinct virus particles. Multipartitism is common among plant viruses, but why this apparently costly genome organization and packaging has evolved remains unclear. Recently Zhang and colleagues developed network epidemiology models to study the epidemic spread of multipartite viruses and their distribution over plant and animal hosts (Phys. Rev. Lett. 2019, 123, 138101). In this short commentary, we call into question the relevance of these results because of key model assumptions. First, the model of plant hosts assumes virus transmission only occurs between adjacent plants. This assumption overlooks the basic but imperative fact that most multipartite viruses are transmitted over variable distances by mobile animal vectors, rendering the model results irrelevant to differences between plant and animal hosts. Second, when not all genome segments of a multipartite virus are transmitted to a host, the model assumes an incessant latent infection occurs. This is a bold assumption for which there is no evidence to date, making the relevance of these results to understanding multipartitism questionable.

    https://doi.org/10.1093/ve/veab004
  • Viruses
    2021

    Metagenomic studies of viruses in weeds and wild plants

    Beata Hasiów-Jaroszewska, Dieke Boezen, Mark Zwart

    High throughput sequencing (HTS) has revolutionised virus detection and discovery, al-lowing for the untargeted characterisation of whole viromes. Viral metagenomics studies have demonstrated the ubiquity of virus infection—often in the absence of disease symptoms—and tend to discover many novel viruses, highlighting the small fraction of virus biodiversity described to date. The majority of the studies using high-throughput sequencing to characterise plant viromes have focused on economically important crops, and only a small number of studies have considered weeds and wild plants. Characterising the viromes of wild plants is highly relevant, as these plants can affect disease dynamics in crops, often by acting as viral reservoirs. Moreover, the viruses in unmanaged systems may also have important effects on wild plant populations and communities. Here, we review metagenomic studies on weeds and wild plants to show the benefits and limita-tions of this approach and identify knowledge gaps. We consider key genomics developments that are likely to benefit the field in the near future. Although only a small number of HTS studies have been performed on weeds and wild plants, these studies have already discovered many novel vi-ruses, demonstrated unexpected trends in virus distributions, and highlighted the potential of met-agenomics as an approach.

    https://doi.org/10.3390/v13101939
  • Proceedings of the Royal Society B: Biological Sciences
    2021

    Chicken gut microbiome members limit the spread of an antimicrobial resistance plasmid in Escherichia coli

    Sarah J. N. Duxbury, Jesse B. Alderliesten, Mark Zwart, Arjan Stegeman, Egil A. J. Fischer, J. Arjan G. M. de Visser
    https://doi.org/10.1098/rspb.2021.2027
  • BMC Microbiology
    2020

    Effect of donor-recipient relatedness on the plasmid conjugation frequency: a meta-analysis

    Jesse B. Alderliesten, Sarah J. N. Duxbury, Mark Zwart, J. Arjan G. M. de Visser, Arjan Stegeman, Egil A. J. Fischer
    Conjugation plays a major role in the transmission of plasmids encoding antibiotic resistance genes in both clinical and general settings. The conjugation efficiency is influenced by many biotic and abiotic factors, one of which is the taxonomic relatedness between donor and recipient bacteria. A comprehensive overview of the influence of donor-recipient relatedness on conjugation is still lacking, but such an overview is important to quantitatively assess the risk of plasmid transfer and the effect of interventions which limit the spread of antibiotic resistance, and to obtain parameter values for conjugation in mathematical models. Therefore, we performed a meta-analysis on reported conjugation frequencies from Escherichia coli donors to various recipient species.
    https://doi.org/10.1186/s12866-020-01825-4
  • Virus Evolution
    2019

    On the stability of sequences inserted into viral genomes

    Anouk Willemsen, Mark Zwart
    Viruses are widely used as vectors for heterologous gene expression in cultured cells or natural hosts, and therefore a large number of viruses with exogenous sequences inserted into their genomes have been engineered. Many of these engineered viruses are viable and express heterologous proteins at high levels, but the inserted sequences often prove to be unstable over time and are rapidly lost, limiting heterologous protein expression. Although virologists are aware that inserted sequences can be unstable, processes leading to insert instability are rarely considered from an evolutionary perspective. Here, we review experimental work on the stability of inserted sequences over a broad range of viruses, and we present some theoretical considerations concerning insert stability. Different virus genome organizations strongly impact insert stability, and factors such as the position of insertion can have a strong effect. In addition, we argue that insert stability not only depends on the characteristics of a particular genome, but that it will also depend on the host environment and the demography of a virus population. The interplay between all factors affecting stability is complex, which makes it challenging to develop a general model to predict the stability of genomic insertions. We highlight key questions and future directions, finding that insert stability is a surprisingly complex problem and that there is need for mechanism-based, predictive models. Combining theoretical models with experimental tests for stability under varying conditions can lead to improved engineering of viral modified genomes, which is a valuable tool for understanding genome evolution as well as for biotechnological applications, such as gene therapy.
    https://doi.org/10.1093/ve/vez045
  • Viruses
    2019

    Identification of loci associated with enhanced virulence in Spodoptera litura nucleopolyhedrovirus isolates using a deep sequencing approach

    Mark Zwart, Ghulam Ali, Elisabeth van Strien, Elio G.W.M. Schijlen, Wopke van der Werf, Just M. Vlak, Manli Wang
    Two genetically distinct Spodoptera litura nucleopolyhedrovirus (SpltNPVs) isolates from Pakistan were investigated by deep sequencing of their full genomes. Previously we reported that isolate SpltNPV-Pak-TAX1 kills S. litura (leafworm) larvae significantly faster than SpltNPV-Pak-BNG. Here we find that the consensus sequences of these two virus isolates shared 99% identity, suggesting they are closely related. The major difference between these two isolates is the absence of hr17 (putative enhancer of transcription and origin of replication) in SpltNPV-Pak-TAX1 and the absence of ORF125 with unknown function in SpltNPV-Pak-BNG. Analysis of the rates of nonsynonymous and synonymous single-nucleotide substitutions showed that strong purifying selection predominates, although for a small number of genes there was neutral or positive selection. The most striking case is ORF122, which encodes a putative viral fibroblast growth factor (FGF), known to be involved in the passage of virus from the midgut to the interior of the larva and linked to virus virulence in other baculoviruses. We found very little polymorphism within both virus isolates, a result at odds with observations for other baculoviruses, possibly suggesting recent dispersal of the virus in Pakistan. We have therefore identified two loci possibly linked to the enhanced virulence of the SpltNPV-Pak-TAX1. This information could help to understand the enhanced activity of SpltNPV-Pak-TAX1 and to select better SpltNPV isolates for the control of S. litura in Pakistan and elsewhere.
    https://doi.org/10.3390/v11090872
  • Viruses
    14-05-2018

    Bioinformatics Meets Virology

    Bashar Ibrahim, Ksenia Arkhipova, Arno C Andeweg, Susana Posada-Céspedes, François Enault, Arthur Gruber, Eugene V Koonin, Anne Kupczok, Philippe Lemey, Alice C McHardy, Dino P McMahon, Brett E Pickett, David L Robertson, Richard H Scheuermann, Alexandra Zhernakova, Mark Zwart, Alexander Schönhuth, Bas E Dutilh, Manja Marz

    The Second Annual Meeting of the European Virus Bioinformatics Center (EVBC), held in Utrecht, Netherlands, focused on computational approaches in virology, with topics including (but not limited to) virus discovery, diagnostics, (meta-)genomics, modeling, epidemiology, molecular structure, evolution, and viral ecology. The goals of the Second Annual Meeting were threefold: (i) to bring together virologists and bioinformaticians from across the academic, industrial, professional, and training sectors to share best practice; (ii) to provide a meaningful and interactive scientific environment to promote discussion and collaboration between students, postdoctoral fellows, and both new and established investigators; (iii) to inspire and suggest new research directions and questions. Approximately 120 researchers from around the world attended the Second Annual Meeting of the EVBC this year, including 15 renowned international speakers. This report presents an overview of new developments and novel research findings that emerged during the meeting.

    https://doi.org/10.3390/v10050256
  • Current Opinion in Virology
    2018

    Population bottlenecks in multicomponent viruses: First forays into the uncharted territory of genome-formula drift

    Serafin Gutiérrez, Mark Zwart
    Multicomponent viral systems face specific challenges when enduring population bottlenecks. These systems can lose coding information due to the lack of co-encapsidation of all the genetic information, at least in a proportion of the capsids in a population. Moreover, bottlenecks can also impact one of the main potential advantages of multicomponent systems: the regulation of gene expression through changes in gene copy frequencies at the population level. How these systems cope with population bottlenecks is far from being clear. Here, two non-exclusive scenarios are described. In the first scenario, population bottlenecks during host infection allow for the isolation of within-host populations with different gene frequencies, leaving the door opened for the selection of populations with adaptive gene frequencies. The second scenario postulates that viruses could influence bottleneck size, at least at certain steps of their life cycle, to limit random changes in gene frequencies. Examples of viral mechanism impacting bottleneck size at cell infection are available and, intriguingly, they can lead to either increases or reductions in bottleneck size. This situation opens the way for putative trade-offs on both gene frequencies and bottleneck sizes that could differ among multicomponent systems.
    https://doi.org/10.1016/j.coviro.2018.09.001
  • Journal of Fish Diseases
    2018

    Quantitative analysis of the dose–response of white spot syndrome virus in shrimp

    Thuy T.N. Ngo, Alistair M. Senior, Antica Culina, Eduardo S.A. Santos, Just M. Vlak, Mark Zwart
    White spot syndrome virus (WSSV) is an important cause of mortality and economiclosses in shrimp farming. Although WSSV‐induced mortality is virus dose dependentand WSSV infection does not necessarily lead to mortality, the relationshipsbetween virus‐particle dose, infection and mortality have not been analysed quanti-tatively. Here, we explored WSSV dose–response by a combination of experiments,modelling and meta‐analysis. We performed dose–response experiments inPenaeusvannameipostlarvae, recorded host mortality and detected WSSV infection. Whenwe fitted infection models to these data, two models—differing in whether theyincorporated heterogeneous host susceptibility to the virus or not—were supportedfor two independent experiments. To determine the generality of these results, wereanalysed published data sets and then performed a meta‐analysis. We found thatWSSV dose–response kinetics is indeed variable over experiments. We could notclearly identify which specific infection model has the most support by meta‐analy-sis, but we argue that these results also are most concordant with a model incorpo-rating varying levels of heterogeneous host susceptibility to WSSV. We haveidentified suitable models for analysing WSSV dose–response, which can elucidatethe most basic virus–host interactions and help to avoid underestimating WSSVinfection at low virus doses.
    https://doi.org/10.1111/jfd.12877
  • Heredity
    2018

    Going, going, gone: predicting the fate of genomic insertions in plant RNA viruses

    Anouk Willemsen, José L. Carrasco, Santiago F. Elena, Mark Zwart
    Horizontal gene transfer is common among viruses, while they also have highly compact genomes and tend to lose artificial genomic insertions rapidly. Understanding the stability of genomic insertions in viral genomes is therefore relevant for explaining and predicting their evolutionary patterns. Here, we revisit a large body of experimental research on a plant RNA virus, tobacco etch potyvirus (TEV), to identify the patterns underlying the stability of a range of homologous and heterologous insertions in the viral genome. We obtained a wide range of estimates for the recombination rate—the rate at which deletions removing the insertion occur—and these appeared to be independent of the type of insertion and its location. Of the factors we considered, recombination rate was the best predictor of insertion stability, although we could not identify
    the specific sequence characteristics that would help predict insertion instability. We also considered experimentally the possibility that functional insertions lead to higher mutational robustness through increased redundancy. However, our observations suggest that both functional and non-functional increases in genome size decreased the mutational robustness. Our results therefore demonstrate the importance of recombination rates for predicting the long-term stability and evolution of viral RNA genomes and suggest that there are unexpected drawbacks to increases in genome size for mutational robustness.
    https://doi.org/10.1038/s41437-018-0086-x
  • Heredity
    2018

    Unraveling the causes of adaptive benefits of synonymous mutations in TEM-1 β-lactamase

    Mark Zwart, Martijn F. Schenk, Sungmin Hwang, A Bertha Koopmanschap, Niek de Lange, Lion van de Pol, Tran Thi Thuy Nga, Ivan G. Szendro, Joachim Krug, Arjan de Visser
    While synonymous mutations were long thought to be without phenotypic consequences, there is growing evidence they can affect gene expression, protein folding, and ultimately the fitness of an organism. In only a few cases have the mechanisms by which synonymous mutations affect the phenotype been elucidated. We previously identified 48 mutations in TEM-1 β-lactamase that increased resistance of Escherichia coli to cefotaxime, 10 of which were synonymous. To better understand the molecular mechanisms underlying the beneficial effect of these synonymous mutations, we made a series of measurements for a panel containing the 10 synonymous together with 10 non-synonymous mutations as a reference. Whereas messenger levels were unaffected, we found that total and functional TEM protein levels were higher for 5 out of 10 synonymous mutations. These observations suggest that some of these mutations act on translation or a downstream process. Similar effects were observed for some small-benefit non-synonymous mutations, suggesting a similar causal mechanism. For the synonymous mutations, we found that the cost of resistance scales with TEM protein levels. A resistance landscape for four synonymous mutations revealed strong epistasis: none of the combinations of mutations exceeded the resistance of the largest-effect mutation and there were synthetically neutral combinations. By considering combined effects of these mutations, we could infer that functional TEM protein level is a multi-dimensional phenotype. These results suggest that synonymous mutations may have beneficial effects by increasing the expression of an enzyme with low substrate activity, which may be realized via multiple, yet unknown, post-transcriptional mechanisms.
    https://doi.org/10.1038/s41437-018-0104-z

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