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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Discovery of inhibitors of bacterial histidine kinases
Velikova, N.R. - \ 2014
Wageningen University. Promotor(en): Jerry Wells, co-promotor(en): A. Marina. - Wageningen : Wageningen University - ISBN 9789462571112 - 225
gastheer-pathogeen interacties - bacteriën - kinasen - histidine - geneesmiddelresistentie - antibiotica - microbiologie - host pathogen interactions - bacteria - kinases - histidine - drug resistance - antibiotics - microbiology
Discovery of Inhibitors of Bacterial Histidine Kinases Summary

The thesis is on novel antibacterial drug discovery (http://youtu.be/NRMWOGgeysM). Using structure-based and fragment-based drug discovery approach, we have identified small-molecule histidine-kinase inhibitors with antibacterial effect against multi-drug resistant strains, including clinical isolates of multi-drug resistant bacteria such as MRSA. Furthermore, we have shown broadening of the antibacterial spectrum and lowering the toxicity of the histidine-kinase inhibitors using nanoparticles. The results open up exciting possibilities for development of novel antibacterial(nano)medicines.

Nutritional zinc deficiency, immune capacity and malaria : a study on mediators of immunity to malaria caused by Plasmodium falciparum in African children
Mbugi, E.V. - \ 2009
Wageningen University. Promotor(en): Huub Savelkoul; J.F. Shao, co-promotor(en): Hans Verhoef. - [S.l. : S.n. - ISBN 9789085855316 - 174
malaria - plasmodium falciparum - immuniteit - zink - kinderen - geneesmiddelresistentie - immuniteitsreactie - mineraaltekorten - voedingsstoffentekorten - cytokinen - antilichamen - endotheel - anemie - tropische ziekten - tanzania - malaria - plasmodium falciparum - immunity - zinc - children - drug resistance - immune response - mineral deficiencies - nutrient deficiencies - cytokines - antibodies - endothelium - anaemia - tropical diseases - tanzania
This thesis aimed at investigating the role of genetic and nutritional factors that affect the immune response to malaria in Tanzanian children. The introductory chapter (Chapter 1) reviews the importance of nutritional deficiencies, particularly of zinc, and presents the hypothesis that such deficiencies lead to impaired immunity and contribute to the burden of malaria. The chapter also describes current efforts to prevent malaria through intermittent preventive treatment, both in infants (IPTi) and pregnant women (IPTp). Sulfadoxinepyrimethamine is still used for first-line treatment of uncomplicated malaria, or, in many countries, to prevent malaria and anaemia in pregnancy. In malaria endemic areas, development of resistance to previously valuable antimalarial drugs has been continuously reported for decades. Thus our initial longitudinal study aimed at measuring the prevalence of resistance-associated mutations on dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes (dhfr and dhps) that confer parasite resistance to sulphadoxinepyrimethamine (SP) that was used as an interim antimalarial drug after chloroquine resistance. Although SP resistance-associated point mutations were highly prevalent, we observed an adequate parasite response to SP (Chapter 2). We speculated that the impact of the dhfr and dhps mutations on SP resistance may be dependent at least in part on the protective immunity that has developed in response to frequent exposure to infection and may be weighed down by host immunity in endemic areas and thus impacts in the continued use of the drug for treatment of malaria. The impact of other drugs with similar mechanisms of action used as antibiotics in selecting mutations responsible for SP resistance needs therefore to be studied for their modulating activity of the immune response. These findings underscore the relevance to further study the crucial involvement of the immune system in the development of protection against malaria but also affecting the efficacy of treatment modalities of malaria in various African conditions.
In the subsequent cross-sectional studies, we assessed the effect of deficiencies of zinc and magnesium as well as iron deficiency anaemia on malaria-specific cytokine responses indicative of innate immunity to Plasmodium falciparum (Chapter 3). In this study, we used Plasmodium falciparum-parasitised red blood cells (pRBCs) as antigens for in vitro stimulation of peripheral blood mononuclear cells (PBMCs). Cytokines were measured in the supernatant of cultured PBMCs after 24 hours of stimulation. Zinc deficiency was associated with a marked increase in monocyte-derived TNF-α concentration in children with malarial infection but not in their uninfected peers. In children with malarial infection, iron deficiency anaemia was associated with elevated concentrations of TNF-α, whereas magnesium deficiency in children without malaria seemed to be associated with increased concentrations of IL-10. Our findings reflected plasticity in cytokine profiles of monocytes reacting to malaria infection under conditions of different nutrient deficiencies. Following the observation of the variable impact of micronutrients on innate cytokines, we evaluated the profile of both type I and type II cytokines and whether they were influenced by nutritional and malaria status (Chapter 4). The cytokine measurements were performed at day 7 of stimulation anticipating that this timing was optimal for measuring effects on these cytokines mainly derived from activated T-cells. The results indicated a variable influence of nutrient deficiencies on increased cytokine response with zinc deficiency and iron deficiency anemia having greater impact on type I and magnesium deficiency on type II cytokines. The subsequent study evaluated the plasma levels of naturally acquired antimalarial antibodies of variousIgG subclasses plus the total IgG and IgM levels and whether they were associated with zinc deficiency based on preceding chapters (Chapter 5). The results indicated a high variability in antibody levels with zinc deficiency, varying with age of the affected child. IgG3 appeared to be predominant across all age subgroups within < 5 yrs aged children providing clues that IgG3 might confer immune protection to malaria under conditions of zinc deficiency. Chapter 6 explored the association between CD36 deficiency, P. falciparum in vitro adherence on purified CD36 and anemia in children. CD36 is a receptor that occurs on the surface of activated immune cells and vascular endothelial cells and participates in phagocytosis and lipid metabolism. We hypothesized that it could play a fundamental role in cytoadherence of erythrocytes that are parasitized by Plasmodium. Our results showed that CD36 deficiency was associated with protection against the development of malarial anemia in children and that it may be mediated through reduced cytoadherence of infected red blood cells to vascular endothelium.
These studies demonstrate that despite antimalarial drug resistance, there is a potential for optimizing the immunological protective capacity in the population to confer parasite clearance that can be variably influenced by micronutrient status. Improving nutritional status in this population could be rewarding not only to increase protection to malaria but possibly also to other infections.
Registratie en monitoring van antibioticumgebruik in dieren
Koene, M.G.J. ; Mevius, D.J. ; Bondt, N. ; Sterrenburg, P. - \ 2009
Lelystad : CVI Wageningen UR (CVI Rapport 09/CVI0009/KOM/sn) - 50
diergezondheid - antibiotica - geneesmiddelresistentie - geneesmiddelen - animal health - antibiotics - drug resistance - drugs
Gebruik antibiotica bij dieren kan zowel bij mens als dier resistentie veroorzaken. Alhoewel er regels zijn voor het gebruik van antibiotica, stijgt het antibioticagebruik toch. Dit onderzoek poogt inzicht te geven in de redenen van het antibioticagebruik
Netwerk antibioticavrij : Het gebruik van antibiotica en antibiotica resistentie!
Animal Sciences Group (ASG), - \ 2007
Lelystad : Animal Sciences Group - 4
veehouderij - antibiotica - geneesmiddelresistentie - diergezondheid - livestock farming - antibiotics - drug resistance - animal health
Informatie van het netwerk antibioticavrij over de risico's van het gebruik van antibiotica in de veehouderij. Een en ander wordt geïllustreerd aan de hand van praktijkvoorbeelden
Antibioticumresistentie in Escherichia coli O 157 geisoleerd tussen 1998 en 2003 in Nederland = Antibiotic resistance in Escherichia coli O157 isolated between 1998 and 2003 in The Netherlands
Roest, H.I.J. ; Liebana, E. ; Wannet, W. ; Duynhoven, Y. van; Veldman, K.T. ; Mevius, D.J. - \ 2007
Tijdschrift voor Diergeneeskunde 132 (2007)24. - ISSN 0040-7453 - p. 954 - 958.
dierhouderij - veehouderij - antibiotica - geneesmiddelresistentie - diervoeding - diergezondheid - voedselveiligheid - escherichia coli - gezondheid - animal husbandry - livestock farming - antibiotics - drug resistance - animal nutrition - animal health - food safety - escherichia coli - health - hemolytic-uremic-syndrome - antimicrobial resistance - integrons - infections - animals - humans - genes - food - vtec
Nederlands: Over het vóórkomen van antibioticumresistentie bij E. coli O157 in Nederland is weinig bekend. In deze studie werden tussen 1998 en 2003 218 humane en 247 niethumane isolaten onderzocht op antibioticumgevoeligheid. Het antibioticumresistentieniveau van E. coli O157 geïsoleerd uit de humane populatie is gemiddeld 5,5 procent en van E. coli O157 geïsoleerd uit de niet-humane populatie gemiddeld 4,0 procent. Deze resistentiepercentages zijn laag vergeleken met de in de literatuur gevonden percentages. In zes multiresistente isolaten werd een klasse 1-integron gevonden. Dit type integron is ook gevonden in commensale E. coli uit landbouwhuisdieren en Salmonella spp. In één van deze integronpositieve isolaten werd naast het ß-lactamasegen blaTEM-1b een ESBLgen uit de CTX-M2-groep aangetoond. Dit is de eerste melding in de literatuur van deze ß-lactamasen in E. coli O157 geïsoleerd uit een kip English: Little is known about the antibiotic resistance of E. coli O157 in the Netherlands. In this study, 218 human and 247 nonhuman samples, isolated between 1998 and 2003, were tested for antimicrobial resistance. About 5.5% of E. coli O157 isolates from human samples were resistant, as were about 4.0% of E. coli O157 isolates from non-human samples. These fi gures are lower than those reported in the literature. Class I integrons were found in six multiresistant isolates. This type of integron is also found in commensal E. coli in food animals and Salmonella spp. One of the integron-positive isolates contained the ß-lactamase blaTEM-1b and an extended spectrum ß-lactamase (ESBL), which belongs to the group 2 CTX-M enzymes. This is the fi rst report of these ß-lactamases in E. coli O157 isolated from chicken
Gevoeligheid voor diverse antibiotica van coagulase negatieve staphylococcen, geisoleerd uit melkmonsters van Nederlands rundvee
Sampimon, O.C. ; Vernooij, J.C.A. ; Mevius, D.J. ; Sol, J. - \ 2007
Tijdschrift voor Diergeneeskunde 132 (2007)7. - ISSN 0040-7453 - p. 200 - 204.
coagulase negative staphylococci - antibiotica - mastitis - rundermastitis - subklinische mastitis - coagulasetest - meervoudige resistentie tegen geneesmiddelen - geneesmiddelenbehandeling - geneesmiddelresistentie - rundvee - coagulase negative staphylococci - antibiotics - mastitis - bovine mastitis - subclinical mastitis - coagulase test - multiple drug resistance - drug therapy - drug resistance - cattle - aureus - susceptibility - herds
During recent years the prevalence of coagulase-negative staphylococci in milk samples from Dutch dairy cows has increased. In 1999 16.2% of the bacteria isolated from milk collected from cows with subclinical mastitis were coagulasenegative staphylococci. In 2004 this proportion was 42.2%. The proportion of coagulase-negative staphylococci of the bacteria isolated from milksamples from cows with clinical mastitis was 7.3% in 1999 and 14.1% in 2004. In this study, the susceptibility of 108 coagulase-negative staphylococci to oxacillin, cefquinome, streptomycin, neomycin, penicillin, and the combination of nafcillin, penicillin, and streptomycin was tested. The isolates were cultured from milk collected from cows with mastitis and typed using the Api-Staph system. Eight species were identifi ed. Staphylococcus chromogenes was the predominant species (41.7%), followed by Staphylococcus xylosus (15.7%) and Staphylococcus simulans (10.2%). With the agar dilution method all strains proved to be sensitive to cefquinome and 90% to oxacillin. Three isolates (2.8%) were mecA-positive. Despite the agar dilution results, these three isolates should be considered resistant to all beta-lactam antibiotics (penicillins, penicillins combined with a beta-lactamase inhibitor and all generations of cephalosporins). In the agar diffusion test, all isolates proved to be sensitive to the combination of nafcillin-penicillin-streptomycin, 99% were sensitive to neomycin and 1% intermediate sensitive, and 95% were sensitive to streptomycin, 4% resistant, and 1% intermediate sensitive. The coagulase-negative staphylococci were highly resistant to penicillin (37.4%), although the level of resistance varied between species, from 0% for Staphylococcus simulans to 100% for taphylococcus saprophyticus. Because coagulase-negative staphylococci are resistant to several antibiotics, sensitivity testing is important for targeted treatment of mastitis
Stenotrophomonas maltophilia: a new potential biocontrol agent of Ralstonia solanacearum, causal agent of potato brown rot
Messiha, N.A.S. ; Diepeningen, A.D. van; Farag, N.S. ; Abdallah, S.A. ; Janse, J.D. ; Bruggen, A.H.C. van - \ 2007
European Journal of Plant Pathology 118 (2007)3. - ISSN 0929-1873 - p. 211 - 225.
geneesmiddelresistentie - antibiotica - biologische bestrijding - zware kleigronden - bedrijfsvoering - stenotrophomonas maltophilia - ralstonia solanacearum - aardappelen - biotesten - antagonisten - drug resistance - antibiotics - biological control - clay soils - management - stenotrophomonas maltophilia - ralstonia solanacearum - potatoes - bioassays - antagonists - biological-control - pseudomonas-solanacearum - bacterial wilt - fluorescent pseudomonads - eucalyptus-urophylla - erwinia-carotovora - pythium-ultimum - rhizosphere - soils - survival
Stenotrophomonas maltophilia was isolated from the rhizosphere of eggplant in the Nile Delta of Egypt, and its antagonistic potential against Ralstonia solanacearum race 3 biovar 2, the causal agent of potato brown rot, was in vitro evaluated on KB agar medium and in vivo on potato plants. In vitro, four isolates of S. maltophilia (PD3531, PD3532, PD3533, and PD3534) appeared antagonistic. The isolate (PD3533) was screened as the most promising antagonist for the in vivo tests. In the greenhouse, the antagonist was applied directly to soil or by bacterization of potato eyepieces. Stenotrophomonas maltophilia significantly suppressed potato brown rot in Egyptian clay soil but not in Dutch clay soil. Survival of a rifampicin and chloramphenicol-resistant S. maltophilia strain PD4560 was investigated in two pairs of clay soils, conventionally and organically managed, from Egypt and the Netherlands. The survival of S. maltophilia was significantly less in Dutch than in Egyptian soils, while the converse occurred for R. solanacearum. These results are in agreement with those obtained in the in vivo biocontrol tests. In conclusion, S. maltophilia may be useful for control of brown rot in the area where it was originally isolated, the Nile Delta in Egypt.
Drug transporters of the fungal wheat pathogen Mycosphaerella graminicola
Roohparvar, R. - \ 2007
Gewasbescherming 38 (2007)4. - ISSN 0166-6495 - p. 160 - 162.
mycosphaerella graminicola - plant pathogens - triticum - wheat - fungal diseases - fungicides - septoria - drug resistance - plantenziekteverwekkers - tarwe - schimmelziekten - fungiciden - geneesmiddelresistentie
Dit proefschirft levert een belangrijke bijdrage aan de wetenschap dat drug transporters een significant rol spelen bij gevoeligheid en (multi)drug-resistentie van schimmels tegen fungiciden. Bij M. graminicola kan de transporter MgMfs1 bijdragen aan een normale fitness van strobilurine-resistente veld-isolaten. Dit inzicht is nieuw en draagt bij tot een beter inzicht in de overlevingskansen van fungiciden-resistente populaties van het pathogeen. Het is niet uitgesloten dat vergelijkbare drug transporters een rol spelen bij resistentie tegen andere specifiek werkende middelen en in andere plantenpathogenen. De rol van de ABC-transporter MgAtr7 met een nog niet eerder beschreven functie in ijzerevenwicht dient nader te worden onderzocht. Het vermogen van niet-fungitoxische modulatoren om plantenziekten te bestrijden is ook niet eerder gepubliceerd. Tot nu toe zijn slechts enkele middelen met een indirecte werking toegelaten voor de bestrijdingvan plantenziekten. Mogelijk kan het uitgevoerde onderzoek dienen als leidraad bij de ontwikkeling van nieuwe ziektewerende middelen met een indirecte werking
Drug transporters of the fungal wheat pathogen Mycosphaerella graminicola
Roohparvar, R. - \ 2007
Wageningen University. Promotor(en): Pierre de Wit, co-promotor(en): Lute Harm Zwiers; M.A. de Waard. - [S.l.] : S.n. - ISBN 9789085046325 - 183
mycosphaerella graminicola - plantenziekteverwekkers - triticum - tarwe - schimmelziekten - fungiciden - septoria - geneesmiddelresistentie - mycosphaerella graminicola - plant pathogens - triticum - wheat - fungal diseases - fungicides - septoria - drug resistance
Examinations priorities in view of the MRSA problem in Dutch animal ownership
Mevius, D.J. ; Verbrugh, H. - \ 2006
Tijdschrift voor Diergeneeskunde 131 (2006)24. - ISSN 0040-7453 - p. 930 - 933.
staphylococcus aureus - geneesmiddelresistentie - antibiotica - dierhouderij - epidemiologie - epidemiologische onderzoeken - ziektedistributie - toegepast onderzoek - staphylococcus aureus - drug resistance - antibiotics - animal husbandry - epidemiology - epidemiological surveys - disease distribution - applied research
Vanaf eind 2005 is het duidelijk geworden dat een MRSA-variant (Methycilline-resistente Staphylococcus aureus) frequent voorkomt in de Nederlandse dierhouderij. Het betreft een klonale verspreiding van het met de Pulsed-Field Gel Electroforese niet typeerbare type MRSA (NT MRSA). Een groep wetenschappers heeft de onderzoeksgebieden geïnventariseerd die nu prioriteit hebben. Een zeer informatief artikel over antibioticum resistentie, een epidemiologisch model, coördinatie van samenwerking tussen organisaties, NT MRSA en de ontwikkeling van veterinaire en humane gezondheidsonderzoeksvragen
Maagdarmwormen : stop met koppelbehandeling
Eysker, M. ; Borgsteede, F.H.M. - \ 2004
Het Schaap 2004 (2004)2. - ISSN 0165-3156 - p. 24 - 27.
haemonchus contortus - trichostrongylidae - nematoda - dierparasitaire nematoden - nematodeninfecties - nematodenbestrijding - wormen - helminthosen - veterinaire helmintologie - anthelmintica - schapen - schapenhouderij - schapenziekten - maagdarmziekten - veterinaire producten - weerstand - geneesmiddelresistentie - geneesmiddelenbehandeling - ziektepreventie - epidemiologie - ziekteoverdracht - diergeneeskunde - veeartsenijkunde - ziektebestrijding - dierziektepreventie - haemonchus contortus - trichostrongylidae - nematoda - animal parasitic nematodes - nematode infections - nematode control - helminths - helminthoses - veterinary helminthology - anthelmintics - sheep - sheep farming - sheep diseases - gastrointestinal diseases - veterinary products - resistance - drug resistance - drug therapy - disease prevention - epidemiology - disease transmission - veterinary science - veterinary medicine - disease control - animal disease prevention
Uitleg over de epidemiologie van maagdarmwormen bij schapen, en adviezen om de ontwikkeling van resistentie tegen wormmiddelen te voorkomen. De huidige praktijk van preventieve behandeling van ooien en lammeren werkt de ontwikkeling van resistentie juist in de hand. Om de selectiedruk voor resistentie bij de wormen te verlagen is het belangrijk om niet meer alle schapen tegelijk te behandelen en wormmiddelen uit de verschillende groepen (benzimidazolen; imidithiazoles; avermectines en milbemycines) af te wisselen. Ook een cocktail van middelen is effectief tegen resistentieontwikkeling
Reducing fitness costs associated with antibiotic resistance: experimental evolution in the filamentous fungus Aspergillus nidulans
Schoustra, S.E. - \ 2004
Wageningen University. Promotor(en): Rolf Hoekstra, co-promotor(en): Fons Debets. - Wageningen : S.n. - ISBN 9085041066 - 142
emericella nidulans - fungicidentolerantie - antibiotica - geneesmiddelresistentie - lysogenie - bacteriocinen - evolutie - genetica - emericella nidulans - fungicide tolerance - antibiotics - drug resistance - lysogeny - bacteriocins - evolution - genetics
Problemen met 'niet pathogene' streptococcen veroorzaakt door influenzavirus?
Vesseur, P. - \ 1997
Praktijkonderzoek varkenshouderij 11 (1997)3. - ISSN 1382-0346 - p. 12 - 12.
diergeneeskunde - varkens - bacterieziekten - micro-organismen - streptococcus - influenza - virusziekten - geneesmiddelresistentie - veterinary science - pigs - bacterial diseases - microorganisms - viral diseases - drug resistance
In de praktijk worden wel eens problemen door Streptococcus suis-typen gevonden die bij nader onderzoek als niet-pathogeen aangemerkt worden.
Het gevoeligheidspatroon van Staphylococcus aureus geïsoleerd uit kwartiermelk van runderen
Vecht, U. ; Wisselink, H.J. ; Vette, H.M.C. - \ 1989
Tijdschrift voor Diergeneeskunde 114 (1989)5. - ISSN 0040-7453 - p. 260 - 269.
antibiotics - antimicrobial properties - dairy cattle - dairy farming - drug resistance - infectious diseases - mammary glands - mastitis - microorganisms - staphylococcus - teats - udders - veterinary science
"Resistance of parasites to anthelmintics" : a workshop in the C.E.C. animal pathology programme, held at the Central Veterinary Institute, Lelystad, The Netherlands, 9 - 10 December 1982
Borgsteede, F.H.M. ; Henriksen, S.A. ; Over, H.J. - \ 1982
Lelystad : Central Veterinary Institute (Facts and reflections no. 4) - 231
geneesmiddelresistentie - helminthosen - micro-organismen - diergeneeskunde - drug resistance - helminthoses - microorganisms - veterinary science
Furazolidone - resistente bacterien
Anonymous, - \ 1971
Wageningen : [s.n.] (Literatuurlijst / Centrum voor landbouwpublikaties en landbouwdocumentatie no. 3285)
bibliografieën - immunologie - furazolidon - geneesmiddelresistentie - bacteriën - bibliographies - immunology - furazolidone - drug resistance - bacteria
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