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.

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    Development of an effective and stable genotype-matched live attenuated newcastle disease virus vaccine based on a novel naturally recombinant malaysian isolate using reverse genetics
    Bello, Muhammad Bashir ; Mahamud, Siti Nor Azizah ; Yusoff, Khatijah ; Ideris, Aini ; Hair-Bejo, Mohd ; Peeters, Ben P.H. ; Omar, Abdul Rahman - \ 2020
    Vaccines 8 (2020)2. - ISSN 2076-393X
    Genotype VII - Genotype-matched - Newcastle disease virus - Recombinant vaccine - Reverse genetics

    Genotype VII Newcastle disease viruses are associated with huge economic losses in the global poultry industry. Despite the intensive applications of vaccines, disease outbreaks caused by those viruses continue to occur frequently even among the vaccinated poultry farms. An important factor in the suboptimal protective efficacy of the current vaccines is the genetic mismatch between the prevalent strains and the vaccine strains. Therefore, in the present study, an effective and stable genotype-matched live attenuated Newcastle disease virus (NDV) vaccine was developed using reverse genetics, based on a recently isolated virulent naturally recombinant NDV IBS025/13 Malaysian strain. First of all, the sequence encoding the fusion protein (F) cleavage site of the virus was modified in silico from virulent polybasic (RRQKRF) to avirulent monobasic (GRQGRL) motif. The entire modified sequence was then chemically synthesized and inserted into pOLTV5 transcription vector for virus rescue. A recombinant virus termed mIBS025 was successfully recovered and shown to be highly attenuated based on OIE recommended pathogenicity assessment indices. Furthermore, the virus was shown to remain stably attenuated and retain the avirulent monobasic F cleavage site after 15 consecutive passages in specific-pathogen-free embryonated eggs and 12 passages in one-day-old chicks. More so, the recombinant virus induced a significantly higher hemagglutination inhibition antibody titre than LaSota although both vaccines fully protected chicken against genotype VII NDV induced mortality and morbidity. Finally, mIBS025 was shown to significantly reduce both the duration and quantity of cloacal and oropharyngeal shedding of the challenged genotype VII virus compared to the LaSota vaccine. These findings collectively indicate that mIBS025 provides a better protective efficacy than LaSota and therefore can be used as a promising vaccine candidate against genotype VII NDV strains.

    Supplementation of lamb diets with vitamin E and rosemary extracts on meat quality parameters
    Leal, Leonel N. ; Beltrán, José A. ; Marc, B. ; Bello, José M. ; Hartog, Leo A. den; Hendriks, Wouter H. ; Martín-Tereso, Javier - \ 2020
    Journal of the Science of Food and Agriculture 100 (2020)7. - ISSN 0022-5142 - p. 2922 - 2931.
    all-rac-α-tocopheryl acetate - colour - lipid oxidation - modified-atmosphere packaging - rosemary extract - vitamin E

    BACKGROUND: Supranutritional supplementation of lamb diets with α-tocopherol is an effective method to reduce lipid oxidation and colour deterioration in meat products. However, alternative antioxidant sources have been proposed to replace the supranutritional vitamin E applications. RESULTS: Indoor concentrate-fed Rasa Aragonesa male lambs (n = 480) were supplemented with increasing levels of all-rac-α-tocopheryl acetate (0.25, 0.5, 1.0 g kg−1 compound feed), rosemary extract (0.20, 0.40, or 0.80 g kg−1 compound feed), or rosemary extract embedded in a fat matrix (0.20, 0.40, or 0.80 g kg−1 compound feed) for 14 days before slaughter. The longissimus thoracis et lumborum muscle from three lambs per pen (18 lambs per treatment) were modified-atmosphere packaged (70% O2 + 30% CO2) and maintained under retail conditions for 14 days. Supranutritional supplementation with antioxidants had no effect (P > 0.05) on average daily weight gain, feed intake, and feed efficiency. Rosemary extract supplementation (with or without fat embedment) had no effect on lipid oxidation, myoglobin forms, or colour stability parameters, regardless of the dose. All vitamin E supplementation levels significantly affected lipid oxidation, colour stability (L*, C*, and h), myoglobin forms, and meat discoloration parameters compared with non-supplemented lambs. CONCLUSIONS: This study demonstrates that, unlike vitamin E, neither dose nor protection of the rosemary extract had an effect on lipid oxidation or meat colour stability of lambs during the 14 days of storage under retail conditions.

    Exploring the prospects of engineered Newcastle disease virus in modern vaccinology
    Bashir Bello, Muhammad ; Yusoff, Khatijah ; Ideris, Aini ; Hair-Bejo, Mohd ; Hassan Jibril, Abdurrahman ; Peeters, Ben P.H. ; Rahman Omar, Abdul - \ 2020
    Viruses 12 (2020)4. - ISSN 1999-4915
    Cancer - Infectious diseases - Newcastle disease virus - Reverse genetics - Vaccines

    Many traditional vaccines have proven to be incapable of controlling newly emerging infectious diseases. They have also achieved limited success in the fight against a variety of human cancers. Thus, innovative vaccine strategies are highly needed to overcome the global burden of these diseases. Advances in molecular biology and reverse genetics have completely restructured the concept of vaccinology, leading to the emergence of state-of-the-art technologies for vaccine design, development and delivery. Among these modern vaccine technologies are the recombinant viral vectored vaccines, which are known for their incredible specificity in antigen delivery as well as the induction of robust immune responses in the vaccinated hosts. Although a number of viruses have been used as vaccine vectors, genetically engineered Newcastle disease virus (NDV) possesses some useful attributes that make it a preferable candidate for vectoring vaccine antigens. Here, we review the molecular biology of NDV and discuss the reverse genetics approaches used to engineer the virus into an efficient vaccine vector. We then discuss the prospects of the engineered virus as an efficient vehicle of vaccines against cancer and several infectious diseases of man and animals.

    Fusarium spp. in Loggerhead Sea Turtles (Caretta caretta): From Colonization to Infection
    Cafarchia, Claudia ; Paradies, Romina ; Figueredo, Luciana A. ; Iatta, Roberta ; Desantis, Salvatore ; Bello, Antonio Vito Francesco Di; Zizzo, Nicola ; Diepeningen, Anne D. van - \ 2020
    Veterinary Pathology 57 (2020)1. - ISSN 0300-9858 - p. 139 - 146.
    bycatch - Caretta caretta - conservation - Fusarium - infection - loggerhead sea turtles - rehabilitation - skin

    With the aim of evaluating the presence of Fusarium spp. in sea turtles with and without lesions and assessing the risk factors favoring colonization and/or infection, 74 loggerhead sea turtles (Caretta caretta) admitted to rescue and rehabilitation clinics in Italy were analyzed. The study compared 31 individuals with no apparent macroscopic lesions and 43 individuals with macroscopic lesions. Shell and skin samples were analyzed using Calcofluor white with 10% potassium hydroxide, standard histopathological examination, and fungal cultures. Fusarium spp. were isolated more frequently from animals with superficial lesions (39%) than from those with no macroscopic lesions (16%). Isolates from animals with superficial lesions were Fusarium solani species complex (FSSC) lineages haplotypes 9, 12, and 27 (unnamed lineages), FSSC-2 (Fusarium keratoplasticum), Fusarium oxysporum (27%), and Fusarium brachygibbosum (3%). In contrast, only F. solani haplotypes 9 and 12 were isolated from animals with no macroscopic lesions. The presence of lesions was identified as a risk factor for the occurrence of Fusarium spp. Of the 74 animals, only 7 (9.5%) scored positive on microscopic examination with Calcofluor, and histological examination of those 7 animals revealed necrosis, inflammatory cells, and fungal hyphae in the carapace and skin. The results of this study suggest that fusariosis should be included in the differential diagnosis of shell and skin lesions in sea turtles. Direct examination using Calcofluor and potassium hydroxide was not useful to diagnose the infection. Histopathological examination and fungal culture should be performed to ensure correct treatment and infection control.

    High throughput cultivation-based screening on the MicroDish platform allows targeted isolation of antibiotic resistant human gut bacteria
    Versluis, Dennis ; Bello Gonzalez, Teresita ; Zoetendal, Erwin ; Passel, Mark van; Smidt, Hauke - \ 2019
    Wageningen University
    PRJEB27463 - ERP109543
    The emergence of bacterial pathogens that are resistant to clinical antibiotics poses an increasing risk to human health. An important reservoir from which bacterial pathogens can acquire resistance is the human gut microbiota. However, thus far, a substantial fraction of the gut microbiota remains uncultivated and has been little-studied with respect to its resistance reservoir-function. Here, we aimed to isolate yet uncultivated resistant gut bacteria by a targeted approach. Therefore, faecal samples from 20 intensive care patients who had received the prophylactic antibiotic treatment selective digestive decontamination (SDD), i.e. tobramycin, polymyxin E, amphotericin B and cefotaxime, were inoculated anaerobically on MicroDish porous aluminium oxide chips placed on top of poor and rich agar media, including media supplemented with the SDD antibiotics. Biomass growing on the chips was analysed by 16S rRNA gene amplicon sequencing, showing large inter-individual differences in bacterial cultivability, and enrichment of a range of taxonomically diverse operational taxonomic units (OTUs). Furthermore, growth of Ruminococcaceae (2 OTUs), Enterobacteriaceae (6 OTUs) and Lachnospiraceae (4 OTUs) was significantly inhibited by the SDD antibiotics. Strains belonging to 16 OTUs were candidates for cultivation to pure culture as they shared ≤95% sequence identity with the closest type strain and had a relative abundance of ≥2%. Six of these OTUs were detected on media containing SDD antibiotics, and as such were prime candidates to be studied regarding antibiotic resistance. One of these six OTUs was obtained in pure culture using targeted isolation. This novel strain was resistant to the antibiotics metrodinazole and imipenem. It was initially classified as member of the Ruminococcaceae, though later it was found to share 99% nucleotide identity with the recently published Sellimonas intestinalis BR72T. In conclusion, we show that high-throughput screening of growth communities can guide targeted isolation of bacteria that serve as reservoirs of antibiotic resistance.
    Manifold learning for parameter reduction
    Holiday, Alexander ; Kooshkbaghi, Mahdi ; Bello-Rivas, Juan M. ; William Gear, C. ; Zagaris, Antonios ; Kevrekidis, Ioannis G. - \ 2019
    Journal of computational physics 392 (2019). - ISSN 0021-9991 - p. 419 - 431.
    Data driven perturbation theory - Data mining - Diffusion maps - Model reduction - Parameter sloppiness

    Large scale dynamical systems (e.g. many nonlinear coupled differential equations)can often be summarized in terms of only a few state variables (a few equations), a trait that reduces complexity and facilitates exploration of behavioral aspects of otherwise intractable models. High model dimensionality and complexity makes symbolic, pen–and–paper model reduction tedious and impractical, a difficulty addressed by recently developed frameworks that computerize reduction. Symbolic work has the benefit, however, of identifying both reduced state variables and parameter combinations that matter most (effective parameters, “inputs”); whereas current computational reduction schemes leave the parameter reduction aspect mostly unaddressed. As the interest in mapping out and optimizing complex input–output relations keeps growing, it becomes clear that combating the curse of dimensionality also requires efficient schemes for input space exploration and reduction. Here, we explore systematic, data-driven parameter reduction by means of effective parameter identification, starting from current nonlinear manifold-learning techniques enabling state space reduction. Our approach aspires to extend the data-driven determination of effective state variables with the data-driven discovery of effective model parameters, and thus to accelerate the exploration of high-dimensional parameter spaces associated with complex models.

    Dietary supplementation of 11 different plant extracts on the antioxidant capacity of blood and selected tissues in lightweight lambs
    Leal, Leonel N. ; Jordán, María J. ; Bello, José M. ; Otal, Julio ; Hartog, Leo A. den; Hendriks, Wouter H. ; Martín-Tereso, Javier - \ 2019
    Journal of the Science of Food and Agriculture 99 (2019)9. - ISSN 0022-5142 - p. 4296 - 4303.
    kidney - lambs - liver - muscle - plant extracts - plasma

    BACKGROUND: Due to the growing public concern regarding the addition of chemical antioxidants to foods, focus has shifted towards natural alternatives. Because of their antioxidant potential, culinary herbs and spices have long been used to extend the shelf-life of foods. However, a better understanding of the fate of these products following intake is required to assess their use in lamb diets. RESULTS: Two hundred and eighty-eight Rasa Aragonesa male lambs (70 days old) were supplemented (5.0 g kg −1 compound feed) with bay, marjoram, oregano, rosemary, thyme, turmeric, cumin, caraway, dill, cinnamon and nutmeg extracts for 14 days before slaughter. Dietary supplementation with plant extracts had no effect on intake, growth performance or antioxidant activity in blood (TEAC values). In muscle, nutmeg supplementation increased (P < 0.05) the radical-scavenging capacity (TEAC), whereas a decrease in the radical-scavenging capacity was found for lambs supplemented with oregano, dill, cinnamon and nutmeg (ORAC values). In liver, nutmeg supplementation increased (P < 0.05) the antioxidant capacity (TEAC), whereas bay (ORAC), turmeric, cinnamon and nutmeg (DPPH values) decreased (P < 0.05) the radical-scavenging capacity of the tissue. In kidney, a lower (P < 0.05) radical-scavenging capacity (TEAC values) was found in lambs supplemented with oregano, cumin and caraway, whereas, turmeric, cumin, caraway, cinnamon and nutmeg increased (P < 0.05) the antioxidant capacity (ORAC values) in kidney. CONCLUSION: Supplementation of lamb diets with plant extracts affected radical-scavenging activity in muscle, liver and kidney. However, due to the divergent results of the different assays for the same tissue, it is not advisable to discriminate plant extracts using this approach.

    High throughput cultivation-based screening on porous aluminum oxide chips allows targeted isolation of antibiotic resistant human gut bacteria
    Versluis, Dennis ; J. Bello González, Teresita de; Zoetendal, Erwin G. ; Passel, Mark W.J. van; Smidt, Hauke - \ 2019
    PLoS ONE 14 (2019)1. - ISSN 1932-6203

    The emergence of bacterial pathogens that are resistant to clinical antibiotics poses an increasing risk to human health. An important reservoir from which bacterial pathogens can acquire resistance is the human gut microbiota. However, thus far, a substantial fraction of the gut microbiota remains uncultivated and has been little-studied with respect to its resistance reservoir-function. Here, we aimed to isolate yet uncultivated resistant gut bacteria by a targeted approach. Therefore, faecal samples from 20 intensive care patients who had received the prophylactic antibiotic treatment selective digestive decontamination (SDD), i.e. tobramycin, polymyxin E, amphotericin B and cefotaxime, were inoculated anaerobically on porous aluminium oxide chips placed on top of poor and rich agar media, including media supplemented with the SDD antibiotics. Biomass growing on the chips was analysed by 16S rRNA gene amplicon sequencing, showing large inter-individual differences in bacterial cultivability, and enrichment of a range of taxonomically diverse operational taxonomic units (OTUs). Furthermore, growth of Ruminococcaceae (2 OTUs), Enterobacteriaceae (6 OTUs) and Lachnospiraceae (4 OTUs) was significantly inhibited by the SDD antibiotics. Strains belonging to 16 OTUs were candidates for cultivation to pure culture as they shared 95% sequence identity with the closest type strain and had a relative abundance of 2%. Six of these OTUs were detected on media containing SDD antibiotics, and as such were prime candidates to be studied regarding antibiotic resistance. One of these six OTUs was obtained in pure culture using targeted isolation. This novel strain was resistant to the antibiotics metrodinazole and imipenem. It was initially classified as member of the Ruminococcaceae, though later it was found to share 99% nucleotide identity with the recently published Sellimonas intestinalis BR72T. In conclusion, we show that high-throughput cultivation-based screening of microbial communities can guide targeted isolation of bacteria that serve as reservoirs of antibiotic resistance.

    Bioavailability of α-tocopherol stereoisomers in lambs depends on dietary doses of all-rac- or RRR-α-tocopheryl acetate
    Neto Leal, Leonel ; Jensen, S.K. ; Bello, J.M. ; Hartog, L.A. den; Hendriks, W.H. ; Martín-Tereso, Javier - \ 2019
    Animal 13 (2019)9. - ISSN 1751-7311 - p. 1874 - 1882.
    When supplementing lamb diets with vitamin E, an equivalence factor of 1.36 is used to discriminate between RRR-α-tocopheryl acetate and all-rac-α tocopheryl acetate. However, more recent studies suggest a need for new equivalence factors for livestock animals. The current study aimed to determine the effect of RRR- and all-rac-α-tocopheryl acetate supplementation on α-tocopherol deposition in lamb tissues. A total of 108 Rasa Aragonesa breed lambs were fed increasing amounts of all-rac-α-tocopheryl acetate (0.25, 0.5, 1.0 and 2.0 g/kg compound feed) or RRR-α-tocopheryl acetate (0.125, 0.25, 0.5 and 1.0 g/kg compound feed) by adding them to a basal diet that contained 0.025 g/kg feed of all-rac-α-tocopheryl acetate as part of the standard vitamin and mineral mixture. The diets were fed for the last 14 days before slaughtering at 25.8 ± 1.67 kg BW. Within 20 min after slaughter samples of muscle, heart, liver, brain and spleen were frozen at −20°C until α-tocopherol analysis. Increased supplementation of either vitamin E sources led to a significant increase ( P<0.001) in α-tocopherol concentration in all tissues studied. The tissue with the highest α-tocopherol concentration was the liver followed by spleen, heart and muscle. At similar supplementation levels (0.25, 0.50 and 1.0 g/kg compound feed), α-tocopherol content in the selected tissues was not affected by α-tocopherol source. However, the ratios between RRR- and all-rac α-tocopheryl acetate increased with the increasing α-tocopherol supplementation (at 0.25 and 1.0 g/kg compound feed), from 1.06 to 1.16 in muscle, 1.07 to 1.15 in heart, 0.91 to 0.94 in liver and 0.98 to 1.10 in spleen. The highest relative proportion of Ʃ2S (sum of SSS-, SSR-, SRS- and SRR-α tocopherol)-configured stereoisomers was found in the liver of lambs supplemented with all-rac-α-tocopheryl acetate accounting for up to 35 to 39% of the total α-tocopherol retained, whereas the proportion of Ʃ2S-configured stereoisomers in the other tissues accounted for <14%. Increasing all-rac-α-tocopheryl acetate supplementation was also found to affect the 2R-configured stereoisomer profile in muscle, heart and spleen with increasing proportions of RRS-, RSR- and RSS- at the cost of RRR-α-tocopherol. In all tissues, the relative proportion of all non-RRR-stereoisomers in lambs receiving RRR-α-tocopheryl acetate was lower than RRR-α-tocopherol. These results confirm that the relative bioavailability of RRR- and all-rac-α-tocopheryl acetate is dose- and tissue-dependent and that a single ratio to discriminate the two sources cannot be used.
    Genotype Diversity of Newcastle Disease Virus in Nigeria : Disease Control Challenges and Future Outlook
    Bello, Muhammad Bashir ; Yusoff, Khatijah Mohd ; Ideris, Aini ; Hair-Bejo, Mohd ; Peeters, Ben P.H. ; Jibril, Abdurrahman Hassan ; Tambuwal, Farouk Muhammad ; Omar, Abdul Rahman - \ 2018
    Advances in Virology 2018 (2018). - ISSN 1687-8639

    Newcastle disease (ND) is one of the most important avian diseases with considerable threat to the productivity of poultry all over the world. The disease is associated with severe respiratory, gastrointestinal, and neurological lesions in chicken leading to high mortality and several other production related losses. The aetiology of the disease is an avian paramyxovirus type-1 or Newcastle disease virus (NDV), whose isolates are serologically grouped into a single serotype but genetically classified into a total of 19 genotypes, owing to the continuous emergence and evolution of the virus. In Nigeria, molecular characterization of NDV is generally very scanty and majorly focuses on the amplification of the partial F gene for genotype assignment. However, with the introduction of the most objective NDV genotyping criteria which utilize complete fusion protein coding sequences in phylogenetic taxonomy, the enormous genetic diversity of the virus in Nigeria became very conspicuous. In this review, we examine the current ecological distribution of various NDV genotypes in Nigeria based on the available complete fusion protein nucleotide sequences (1662 bp) in the NCBI database. We then discuss the challenges of ND control as a result of the wide genetic distance between the currently circulating NDV isolates and the commonest vaccines used to combat the disease in the country. Finally, we suggest future directions in the war against the economically devastating ND in Nigeria.

    Diagnostic and Vaccination Approaches for Newcastle Disease Virus in Poultry : The Current and Emerging Perspectives
    Bello, Muhammad Bashir ; Yusoff, Khatijah ; Ideris, Aini ; Hair-Bejo, Mohd ; Peeters, Ben P.H. ; Omar, Abdul Rahman - \ 2018
    BioMed Research International 2018 (2018). - ISSN 2314-6133 - 18 p.

    Newcastle disease (ND) is one of the most devastating diseases that considerably cripple the global poultry industry. Because of its enormous socioeconomic importance and potential to rapidly spread to naïve birds in the vicinity, ND is included among the list of avian diseases that must be notified to the OIE immediately upon recognition. Currently, virus isolation followed by its serological or molecular identification is regarded as the gold standard method of ND diagnosis. However, this method is generally slow and requires specialised laboratory with biosafety containment facilities, making it of little relevance under epidemic situations where rapid diagnosis is seriously needed. Thus, molecular based diagnostics have evolved to overcome some of these difficulties, but the extensive genetic diversity of the virus ensures that isolates with mutations at the primer/probe binding sites escape detection using these assays. This diagnostic dilemma leads to the emergence of cutting-edge technologies such as next-generation sequencing (NGS) which have so far proven to be promising in terms of rapid, sensitive, and accurate recognition of virulent Newcastle disease virus (NDV) isolates even in mixed infections. As regards disease control strategies, conventional ND vaccines have stood the test of time by demonstrating track record of protective efficacy in the last 60 years. However, these vaccines are unable to block the replication and shedding of most of the currently circulating phylogenetically divergent virulent NDV isolates. Hence, rationally designed vaccines targeting the prevailing genotypes, the so-called genotype-matched vaccines, are highly needed to overcome these vaccination related challenges. Among the recently evolving technologies for the development of genotype-matched vaccines, reverse genetics-based live attenuated vaccines obviously appeared to be the most promising candidates. In this review, a comprehensive description of the current and emerging trends in the detection, identification, and control of ND in poultry are provided. The strengths and weaknesses of each of those techniques are also emphasised.

    Taxonomy of the family Arenaviridae and the order Bunyavirales : update 2018
    Maes, Piet ; Alkhovsky, Sergey V. ; Bào, Yīmíng ; Beer, Martin ; Birkhead, Monica ; Briese, Thomas ; Buchmeier, Michael J. ; Calisher, Charles H. ; Charrel, Rémi N. ; Choi, Il Ryong ; Clegg, Christopher S. ; Torre, Juan Carlos de la; Delwart, Eric ; DeRisi, Joseph L. ; Bello, Patrick L. Di; Serio, Francesco Di; Digiaro, Michele ; Dolja, Valerian V. ; Drosten, Christian ; Druciarek, Tobiasz Z. ; Du, Jiang ; Ebihara, Hideki ; Elbeaino, Toufic ; Gergerich, Rose C. ; Gillis, Amethyst N. ; Gonzalez, Jean Paul J. ; Haenni, Anne Lise ; Hepojoki, Jussi ; Hetzel, Udo ; Hồ, Thiện ; Hóng, Ní ; Jain, Rakesh K. ; Jansen van Vuren, Petrus ; Jin, Qi ; Jonson, Miranda Gilda ; Junglen, Sandra ; Keller, Karen E. ; Kemp, Alan ; Kipar, Anja ; Kondov, Nikola O. ; Koonin, Eugene V. ; Kormelink, Richard ; Korzyukov, Yegor ; Krupovic, Mart ; Lambert, Amy J. ; Laney, Alma G. ; LeBreton, Matthew ; Lukashevich, Igor S. ; Marklewitz, Marco ; Markotter, Wanda ; Martelli, Giovanni P. ; Martin, Robert R. ; Mielke-Ehret, Nicole ; Mühlbach, Hans Peter ; Navarro, Beatriz ; Ng, Terry Fei Fan ; Nunes, Márcio Roberto Teixeira ; Palacios, Gustavo ; Pawęska, Janusz T. ; Peters, Clarence J. ; Plyusnin, Alexander ; Radoshitzky, Sheli R. ; Romanowski, Víctor ; Salmenperä, Pertteli ; Salvato, Maria S. ; Sanfaçon, Hélène ; Sasaya, Takahide ; Schmaljohn, Connie ; Schneider, Bradley S. ; Shirako, Yukio ; Siddell, Stuart ; Sironen, Tarja A. ; Stenglein, Mark D. ; Storm, Nadia ; Sudini, Harikishan ; Tesh, Robert B. ; Tzanetakis, Ioannis E. ; Uppala, Mangala ; Vapalahti, Olli ; Vasilakis, Nikos ; Walker, Peter J. ; Wáng, Guópíng ; Wáng, Lìpíng ; Wáng, Yànxiăng ; Wèi, Tàiyún ; Wiley, Michael R. ; Wolf, Yuri I. ; Wolfe, Nathan D. ; Wú, Zhìqiáng ; Xú, Wénxìng ; Yang, Li ; Yāng, Zuòkūn ; Yeh, Shyi Dong ; Zhāng, Yǒng Zhèn ; Zhèng, Yàzhōu ; Zhou, Xueping ; Zhū, Chénxī ; Zirkel, Florian ; Kuhn, Jens H. - \ 2018
    Archives of Virology 163 (2018)8. - ISSN 0304-8608 - p. 2295 - 2310.
    In 2018, the family Arenaviridae was expanded by inclusion of 1 new genus and 5 novel species. At the same time, the recently established order Bunyavirales was expanded by 3 species. This article presents the updated taxonomy of the family Arenaviridae and the order Bunyavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future.
    Dietary vitamin E dosage and source affects meat quality parameters in light weight lambs
    Leal, Leonel N. ; Beltrán, José A. ; Alonso, Verónica ; Bello, José M. ; Hartog, Leo A. den; Hendriks, Wouter H. ; Martín-Tereso, Javier - \ 2018
    Journal of the Science of Food and Agriculture 98 (2018)4. - ISSN 0022-5142 - p. 1606 - 1614.
    all-rac-α-tocopheryl acetate - colour - lipid oxidation - modified atmosphere packaging - RRR-α-tocopheryl acetate - vitamin E
    BACKGROUND: Supra-nutritional vitamin E supplementation is a commonly used approach to delay lipid oxidation and colour deterioration in lamb and beef meat marketed under modified atmosphere packaging. However, these applications lack a precise calibration of dose for the desired effect and, in addition, limited information is available regarding the use of natural vitamin E for this purpose. RESULTS: Three hundred and sixty Rasa Aragonesa lambs were fed diets supplemented with all-rac-α-tocopheryl acetate (250, 500, 1000 and 2000 mg kg–1 compound feed), RRR-α-tocopheryl acetate (125, 250, 500 and 1000 mg kg–1 compound feed) and a basal diet without vitamin E supplementation for 14 days before slaughter at 25.8 ± 1.67 kg body weight. Vitamin E supplementation had no effect (P > 0.05) on average daily weight gain, feed intake and feed efficiency. Display time had larger effects on lipid oxidation, colour stability, myoglobin forms and meat discolouration parameters compared to vitamin E supplementation. However, vitamin E source and dosage significantly extended meat shelf-life as indicated by lipid oxidation, redness, hue angle, metmyoglobin formation, deoxymyoglobin formation, A580–630 and ISO2. CONCLUSION: The quantification of these effects demonstrated that the biological activity value of 1.36 used to distinguish both vitamin E sources is not appropriate for meat quality enhancing properties.
    Supplementation of natural or synthetic vitamin E on α-tocopherol concentration in lamb tissues
    Neto Leal, Leonel ; Jensen, S.K. ; Bello, J.M. ; Hartog, L.A. den; Hendriks, W.H. ; Martín-Tereso, Javier - \ 2017
    In: Book of Abstracts of the 68th Annual Meeting of the European Federation of Animal Science. - Wageningen : Wageningen Academic Publishers (Book of abstracts 23) - ISBN 9789086863129 - p. 355 - 355.
    Comparative gut microbiota and resistome profiling of intensive care patients receiving selective digestive tract decontamination and healthy subjects
    Buelow, Elena ; Bello González, Teresita D.J. ; Fuentes, Susana ; Steenhuijsen Piters, Wouter A.A. de; Lahti, Leo ; Bayjanov, Jumamurat R. ; Majoor, Eline A.M. ; Braat, Johanna C. ; Mourik, Maaike S.M. van; Oostdijk, Evelien A.N. ; Willems, Rob J.L. ; Bonten, Marc J.M. ; Passel, Mark W.J. van; Smidt, Hauke ; Schaik, Willem van - \ 2017
    Microbiome 5 (2017)1. - ISSN 2049-2618 - p. 88 - 88.
    Anti-bacterial agents - Antibiotic prophylaxis - Drug resistance - Intensive care - Microbial - Microbiome
    BACKGROUND: The gut microbiota is a reservoir of opportunistic pathogens that can cause life-threatening infections in critically ill patients during their stay in an intensive care unit (ICU). To suppress gut colonization with opportunistic pathogens, a prophylactic antibiotic regimen, termed "selective decontamination of the digestive tract" (SDD), is used in some countries where it improves clinical outcome in ICU patients. Yet, the impact of ICU hospitalization and SDD on the gut microbiota remains largely unknown. Here, we characterize the composition of the gut microbiota and its antimicrobial resistance genes ("the resistome") of ICU patients during SDD and of healthy subjects.RESULTS: From ten patients that were acutely admitted to the ICU, 30 fecal samples were collected during ICU stay. Additionally, feces were collected from five of these patients after transfer to a medium-care ward and cessation of SDD. Feces from ten healthy subjects were collected twice, with a 1-year interval. Gut microbiota and resistome composition were determined using 16S rRNA gene phylogenetic profiling and nanolitre-scale quantitative PCRs. The microbiota of the ICU patients differed from the microbiota of healthy subjects and was characterized by lower microbial diversity, decreased levels of Escherichia coli and of anaerobic Gram-positive, butyrate-producing bacteria of the Clostridium clusters IV and XIVa, and an increased abundance of Bacteroidetes and enterococci. Four resistance genes (aac(6')-Ii, ermC, qacA, tetQ), providing resistance to aminoglycosides, macrolides, disinfectants, and tetracyclines, respectively, were significantly more abundant among ICU patients than in healthy subjects, while a chloramphenicol resistance gene (catA) and a tetracycline resistance gene (tetW) were more abundant in healthy subjects.CONCLUSIONS: The gut microbiota of SDD-treated ICU patients deviated strongly from the gut microbiota of healthy subjects. The negative effects on the resistome were limited to selection for four resistance genes. While it was not possible to disentangle the effects of SDD from confounding variables in the patient cohort, our data suggest that the risks associated with ICU hospitalization and SDD on selection for antibiotic resistance are limited. However, we found evidence indicating that recolonization of the gut by antibiotic-resistant bacteria may occur upon ICU discharge and cessation of SDD.
    Supplementation of natural or synthetic vitamin E on alpha tocopherol concentration in lamb tissues
    Neto Leal, Leonel ; Jensen, S.K. ; Bello, J.M. ; Hartog, L.A. den; Hendriks, W.H. ; Martin-Tereso, J. - \ 2017
    In: Book of Abstracts of the 68th Annual Meeting of the European Federation of Animal Science. - Wageningen : Wageningen Academic Publishers (Book of abstracts 23) - ISBN 9789086863129 - p. 355 - 355.
    Characterization of Enterococcus isolates colonizing the intestinal tract of intensive care unit patients receiving selective digestive decontamination
    Bello Gonzalez, Teresita D.J. ; Pham, Phu ; Top, Janetta ; Willems, Rob J.L. ; Schaik, Willem van; Passel, Mark W.J. van; Smidt, Hauke - \ 2017
    Frontiers in Microbiology 8 (2017). - ISSN 1664-302X - 10 p.
    Antibiotic prophylactic therapy - Antibiotic resistance - Enterococcus - Intestinal colonization - Selective digestive decontamination - Virulence factors

    Enterococci have emerged as important opportunistic pathogens in intensive care units (ICUs). In this study, enterococcal population size and Enterococcus isolates colonizing the intestinal tract of ICU patients receiving Selective Digestive Decontamination (SDD) were investigated. All nine patients included in the study showed substantial shifts in the enterococcal 16S rRNA gene copy number in the gut microbiota during the hospitalization period. Furthermore, 41 Enterococcus spp. strains were isolated and characterized from these patients at different time points during and after ICU hospitalization, including E. faecalis (n = 13), E. faecium (n = 23), and five isolates that could not unequivocally assigned to a specific species (E. sp. n = 5)Multi locus sequence typing revealed a high prevalence of ST 6 in E. faecalis isolates (46%) and ST 117 in E. faecium (52%). Furthermore, antibiotic resistance phenotypes, including macrolide and vancomycin resistance, as well as virulence factor-encoding genes [asa1, esp-fm, esp-fs, hyl, and cyl (B)] were investigated in all isolates. Resistance to ampicillin and tetracycline was observed in 25 (61%) and 19 (46%) isolates, respectively. Furthermore, 30 out of 41 isolates harbored the erm (B) gene, mainly present in E. faecium isolates (78%). The most prevalent virulence genes were asa1 in E. faecalis (54%) and esp (esp-fm, 74%; esp-fs, 39%). Six out of nine patients developed nosocomial enterococcal infections, however, corresponding clinical isolates were unfortunately not available for further analysis. Our results show that multiple Enterococcus species, carrying several antibiotic resistance and virulence genes, occurred simultaneously in patients receiving SDD therapy, with varying prevalence dynamics over time. Furthermore, simultaneous presence and/or replacement of E. faecium STs was observed-, reinforcing the importance of screening multiple isolates to comprehensively characterize enterococcal diversity in ICU patients.

    Interplay between gut microbiota and antibiotics
    Jesus Bello Gonzalez, Teresita de - \ 2016
    Wageningen University. Promotor(en): Hauke Smidt, co-promotor(en): M.W.J. van Passel. - Wageningen : Wageningen University - ISBN 9789463430043 - 293
    antibiotics - intestinal microorganisms - aminoglycoside antibiotics - enterococcus - interactions - zoo animals - man - patients - dna sequencing - polymerase chain reaction - antibiotica - darmmicro-organismen - aminoglycoside antibiotica - enterococcus - interacties - dierentuindieren - mens - patiënten - dna-sequencing - polymerase-kettingreactie

    The human body is colonized by a vast number of microorganisms collectively defined as the microbiota. In the gut, the microbiota has important roles in health and disease, and can serve as a host of antibiotic resistance genes. Disturbances in the ecological balance, e.g. by antibiotics, can affect the diversity and dynamics of the microbiota. The extent of the disturbance induced by antibiotics is influenced by, among other factors, the class of antibiotic, the dose, and administration route. One of the most common consequences of excessive antibiotic use is the emergence of antibiotic resistant bacteria and the dissemination of the corresponding resistance genes to other microbial inhabitants of the gut community, in addition to affecting the colonization resistance and promoting the overgrowth of pathogens. These effects are particularly relevant for Intensive Care Unit (ICU) patients, which are frequently exposed to a high risk of hospital-acquired infections associated with antibiotic resistant bacteria.

    Due to the important roles that members of the gut microbiota play in the host, including their role as potential hubs for the dissemination of antibiotic resistance, recent research has focused on determining the composition and function of gut microorganisms and the antibiotic resistance genes associated with them.

    The objectives of the research described in this thesis were to study the diversity and dynamics of the gut microbiota and resistome in ICU patients receiving antibiotic prophylactic therapy, and to assess the colonization dynamics with antibiotic resistant bacteria focusing on the commensal microbiota as a reservoir of antibiotic resistance genes by using culture dependent and independent techniques. Furthermore, the genetic background involved in the subsistence phenotype was investigated to disentangle the links between resistance and subsistence.

    Bacteria harbor antibiotic resistance genes that participate in a range of processes such as resisting the toxic effects of antibiotics, but could also aid in the utilization of antibiotics as sole carbon source, referred to as antibiotic subsistence phenotype. In chapter 2, the potential of gut bacteria from healthy human volunteers and zoo animals to subsist on antibiotics was investigated.

    Various gut isolates of Escherichia coli and Cellulosimicrobium spp. displayed the subsistence phenotype, mainly with aminoglycosides. Although no antibiotic degradation could be detected, the number of colony forming units increased during growth in medium with only the antibiotic as a carbon source. By using different approaches to study the aminoglycoside subsistence phenotype, we observed that laboratory strains carrying the aminoglycoside 3’phosphotransferase II gene also displayed the subsistence phenotype on aminoglycosides and that glycosyl-hydrolases seem to be involved in the subsistence phenotype. As the zoo animals for which the subsistence phenotype was investigated also included a number of non-human primates, the applicability of Human Intestinal Tract Chip (HITChip) to study the gut microbiota composition of these animals was assessed, including a comparison with healthy human volunteers (Chapter 3). It was concluded that the HITChip can be successfully applied to the gut microbiota of closely related hominids, and the microbiota dynamics can therefore be quickly assessed by the HITChip.

    In Chapter 4, a combination of 16S rRNA phylogenetic profiling using the HITChip and metagenomics sequencing was implemented on samples from a single ICU hospitalized patient that received antibiotic prophylactic therapy (Selective Digestive Decontamination - SDD). The different approaches showed a highly dynamic microbiota composition over time and the prevalence of aminoglycoside resistance genes harbored by a member of the commensal anaerobic microbiota, highlighting the role of the commensal microbiota as a reservoir of antibiotic resistance genes. As an extension of this study (Chapter 5), 11 ICU patients receiving SDD were followed using 10 healthy individuals as a control group to compare the diversity and dynamics of the gut microbiota and resistome by HITChip and nanolitre-scale quantitative PCRs, respectively. The microbial diversity of the healthy individuals was higher compared to ICU patients, and it was less dynamic compared to ICU patients under antibiotic treatment. Likewise, the levels of antibiotic resistance genes increased in ICU patients compared to healthy individuals, indicating that during ICU hospitalization and the SDD, gut microbiota diversity and dynamics are profoundly affected, including the selection of antibiotic resistance in anaerobic commensal bacteria.

    This was further expanded in an extensive study focusing on colonization dynamics with antibiotic resistant bacteria as described in Chapter 6. This was performed in the same group of ICU-hospitalized patients receiving SDD therapy and showed that by using a range of culture media and selective conditions a variety of taxonomic groups could be isolated, including aerobic and anaerobic antibiotic resistant bacteria. The overall composition of the faecal microbiota detected by HITChip indicated mainly a decrease of Enterobacteriaceae and an increase of the enterococcal population. Since critically ill patients are susceptible to hospital-acquired infections and the control of the emergence of antibiotic resistance is crucial to improve therapeutic outcomes, an extended analysis of the Enterococcus colonization dynamics in this group of patients by cultivation and phenotypic and genotypic characterization of the isolates provided new information about carriage of antibiotic resistance and virulence factor encoding genes (Chapter 7). It also highlighted the opportunity for the exchange of resistance and virulence genes, which could increase the risk of acquiring nosocomial infections.

    Next, chapter 8 described the implementation of high-throughput cultivation-based screening using the Microdish platform combined with high-throughput sequencing (MiSeq) using faecal samples from ICU patients receiving SDD. This allowed for the recovery of previously uncultivable bacteria, including a pure culture of a close relative of Sellimonas intestinalis BR72T that was isolated from media containing tobramycin, cefotaxime and polymyxin E. This strain could therefore represent a potential antibiotic resistance reservoir.

    In conclusion, this thesis provides broad insight into the diversity and dynamics of the gut microbiota and resistome in ICU hospitalized patients receiving SDD therapy as well as the dynamics of colonization with antibiotic resistant bacteria. Especially our extensive study of the colonization dynamics of Enterococcus spp. during ICU stay reinforced the notion that SDD therapy does not cover this group of bacteria and highlights the importance of a critical control of the emergence of antibiotic resistance in enterococci and their spread and dissemination as known potential pathogens.

    Furthermore, the extensive use of antibiotics could select for an increase in the rate of antibiotic resistance against aminoglycosides and beta-lactams, indicating that a control in the use of broad spectrum antibiotics needs to be considered. In addition, this thesis provides evidence regarding the possible genetic background involved in the subsistence phenotype, however, future studies on metabolic pathways could provide novel insight into the underlying mechanisms.

    Study of the aminoglycoside subsistence phenotype of bacteria residing in the gut of humans and zoo animals
    Bello Gonzalez, Teresita ; Zuidema, Tina ; Bor, Gerrit ; Smidt, Hauke ; Passel, M.W.J. van - \ 2016
    Frontiers in Microbiology 6 (2016)JAN. - ISSN 1664-302X - 7 p.
    Aminoglycosides - Antibiotic resistance - Antibiotic subsistence - Antibiotic subsistence phenotype - Single carbon source

    Recent studies indicate that next to antibiotic resistance, bacteria are able to subsist on antibiotics as a carbon source. Here we evaluated the potential of gut bacteria from healthy human volunteers and zoo animals to subsist on antibiotics. Nine gut isolates of Escherichia coli and Cellulosimicrobium sp. displayed increases in colony forming units (CFU) during incubations in minimal medium with only antibiotics added, i.e., the antibiotic subsistence phenotype. Furthermore, laboratory strains of E. coli and Pseudomonas putida equipped with the aminoglycoside 3' phosphotransferase II gene also displayed the subsistence phenotype on aminoglycosides. In order to address which endogenous genes could be involved in these subsistence phenotypes, the broad-range glycosyl-hydrolase inhibiting iminosugar deoxynojirimycin (DNJ) was used. Addition of DNJ to minimal medium containing glucose showed initial growth retardation of resistant E. coli, which was rapidly recovered to normal growth. In contrast, addition of DNJ to minimal medium containing kanamycin arrested resistant E. coli growth, suggesting that glycosyl-hydrolases were involved in the subsistence phenotype. However, antibiotic degradation experiments showed no reduction in kanamycin, even though the number of CFUs increased. Although antibiotic subsistence phenotypes are readily observed in bacterial species, and are even found in susceptible laboratory strains carrying standard resistance genes, we conclude there is a discrepancy between the observed antibiotic subsistence phenotype and actual antibiotic degradation. Based on these results we can hypothesize that aminoglycoside modifying enzymes might first inactivate the antibiotic (i.e., by acetylation of amino groups, modification of hydroxyl groups by adenylation and phosphorylation respectively), before the subsequent action of catabolic enzymes. Even though we do not dispute that antibiotics could be used as a single carbon source, our observations show that antibiotic subsistence should be carefully examined with precise degradation studies, and that its mechanistic basis remains inconclusive.

    Hierarchical Bayesian inference on genetic and non-genetic components of partial efficiencies determining feed efficiency in dairy cattle
    Lu, Y. ; VandeHaar, M.J. ; Spurlock, D.M. ; Weigel, K.A. ; Armentano, L. ; Staples, C.R. ; Connor, E.E. ; Wang, Z. ; Coffey, M. ; Veerkamp, R.F. ; Haas, Y. de; Tempelman, R.J. ; Bello, N. - \ 2015
    Dairy cattle feed efficiency (FE) can be defined as the ability to convert DMI into milk energy (MILKE) and maintenance or metabolic body weight (MBW). In other words, FE is DMI conditional on MILKE and MBW (i.e., DMI|MILKE,MBW). These partial regressions or partial efficiencies (PE) of DMI on MILKE and MBW can be separately partitioned into genetic or residual PE; furthermore, either PE category might be heterogeneous across various environmental or management factors. We develop a hierarchical Bayesian multivariate mixed model to infer upon such heterogeneity in PE as well as that of variance components (VC) of FE by modeling genetic and residual components of PE and of VC as mixed model functions of various factors such as station (fixed), parity (fixed), days in milk (fixed), and ration within station (random). After validating our proposed model with a simulation study, we applied it to analysis of a dairy consortium data set involving 5,088 Holstein cows from 13 research stations in 4 countries. Although no significant differences were detected across stations for the genetic PE of DMI|MILKE (0.38 kg/Mcal) and of DMI|MBW (0.10 kg/kg0.75), as well as the residual PE of DMI|MILKE (0.33 kg/Mcal), the residual PE of DMI|MBW significantly differed across stations (P <0.05), ranging from 0.05 kg/kg0.75 to 0.18 kg/ kg0.75. Substantial heterogeneity in genetic and residual VC in FE across stations, rations, and parities was also inferred. Estimated heritabilities of FE ranged from 0.16 to 0.46 across stations, whereas the overall estimated heritability of FE was 0.23. These results suggest that FE is more complex than what is currently considered in most quantitative genetic analyses.
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