A5064901452- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Synthesis and Biological Evaluation
- Insect symbiosis and bacterial influences
- Parasites and Host Interactions
- Biochemical and Molecular Research
- Monoclonal and Polyclonal Antibodies Research
- Insect and Pesticide Research
- Malaria Research and Control
- Mosquito-borne diseases and control
- HIV/AIDS drug development and treatment
- Synthesis and Catalytic Reactions
- Viral Infections and Vectors
- Calcium signaling and nucleotide metabolism
- Adenosine and Purinergic Signaling
- Vector-borne infectious diseases
- Respiratory viral infections research
- Microbial Natural Products and Biosynthesis
- Crystallization and Solubility Studies
- Galectins and Cancer Biology
- Immune Cell Function and Interaction
- Cancer therapeutics and mechanisms
- X-ray Diffraction in Crystallography
- Glycosylation and Glycoproteins Research
- Macrophage Migration Inhibitory Factor
University of Antwerp
2016-2025
University of Münster
2024
Provincial Institute for Hygiene
2021
Instituut voor Tropische Geneeskunde
2009-2017
VIB-UGent Center for Inflammation Research
2016
Vrije Universiteit Brussel
2002-2015
VIB-VUB Laboratory Myeloid Cell Immunology
2012-2015
Vlaams Instituut voor Biotechnologie
2002-2015
Tsetse flies are the sole vectors of human African trypanosomiasis throughout sub-Saharan Africa. Both sexes adult tsetse feed exclusively on blood and contribute to disease transmission. Notable differences between other include obligate microbial symbioses, viviparous reproduction, lactation. Here, we describe sequence annotation 366-megabase Glossina morsitans genome. Analysis genome 12,308 predicted protein-encoding genes led multiple discoveries, including chromosomal integrations...
Tsetse flies are the sole vectors of Trypanosoma brucei parasites that cause sleeping sickness. Our knowledge on early interface between infective metacyclic forms and mammalian host skin is currently highly limited. Glossina morsitans infected with fluorescently tagged T. were used in this study to initiate natural infections mice. Metacyclic trypanosomes found be infectious through intradermal route sharp contrast blood stream form trypanosomes. Parasite emigration from dermal inoculation...
During the last decade miltefosine (MIL) has been used as first-line treatment for visceral leishmaniasis in endemic areas with antimonial resistance, but a decline clinical effectiveness is now being reported. While only two MIL-resistant Leishmania infantum strains from HIV co-infected patients have documented, phenotypic MIL-resistance L. donovani not yet identified laboratory. Hence, better understanding of factors contributing to increased MIL-treatment failure necessary. Given paucity...
Tsetse flies (Glossina sp.) are the vectors of human and animal trypanosomiasis throughout sub-Saharan Africa. distinguished from other Diptera by unique adaptations, including lactation birthing live young (obligate viviparity), a vertebrate blood-specific diet both sexes, obligate bacterial symbiosis. This work describes comparative analysis six Glossina genomes representing three sub-genera: Morsitans (G. morsitans morsitans, G. pallidipes, austeni), Palpalis palpalis, fuscipes), Fusca...
Tsetse flies are the notorious transmitters of African trypanosomiasis, a disease caused by Trypanosoma parasite that affects humans and livestock on continent. Metacyclic infection rates in natural tsetse populations with brucei, including two human-pathogenic subspecies, very low, even epidemic situations. Therefore, infected fly/host contact frequency is key determinant transmission dynamics. As an obligate blood feeder, rely their complex salivary potion to inhibit host haemostatic...
Abstract African trypanosomiasis is a disease caused by Trypanosoma brucei parasites with limited treatment options. unable to synthesize purines de novo and relies solely on their uptake interconversion from the host, constituting purine nucleoside analogues potential source of antitrypanosomal agents. Here we combine structural elements known trypanocidal develop series 3’-deoxy-7-deazaadenosine nucleosides, investigate effects against trypanosomes. 3’-Deoxytubercidin highly potent...
Visceral leishmaniasis (VL) is a parasitic disease endemic across multiple regions of the world and fatal if untreated. Current therapies are unsuitable, there an urgent need for safe, short-course, low-cost oral treatments to combat this neglected disease. The benzoxaborole chemotype has previously delivered clinical candidates treatment other diseases. Here, we describe development optimization series, leading identification compounds with potent in vitro vivo antileishmanial activity....
Abstract Approximately 20% of sleeping sickness patients exhibit respiratory complications, however, with a largely unknown role the parasite. Here we show that tsetse fly-transmitted Trypanosoma brucei parasites rapidly and permanently colonize lungs occupy extravascular spaces surrounding blood vessels alveoli bronchi. They are present as nests multiplying exhibiting close interactions collagen active secretion extracellular vesicles. The local immune response shows substantial increase...
African trypanosomes of the Trypanosoma brucei species are extracellular protozoan parasites that cause deadly disease trypanosomiasis in humans and contribute to animal counterpart, Nagana. Trypanosome clearance from bloodstream is mediated by antibodies specific for their Variant Surface Glycoprotein (VSG) coat antigens. However, T. infection induces polyclonal B cell activation, clonal exhaustion, sustained depletion mature splenic Marginal Zone (MZB) Follicular (FoB) cells, destruction...
Abstract Background Sodalis glossinidius , a gram-negative bacterial endosymbiont of the tsetse fly, has been proposed as potential in vivo drug delivery vehicle to control trypanosome parasite development an approach known paratransgenesis. Despite this interest S. paratransgenic platform organism flies, few effector molecules have identified so far and date none these successfully expressed bacterium. Results In study, was transformed express single domain antibody, (Nanobody ® ) Nb_An33,...
Sodalis glossinidius, a vertically transmitted microbial symbiont of the tsetse fly, is currently considered as potential delivery system for anti-trypanosomal components that reduce or eliminate capability fly host to transmit parasitic trypanosomes, an approach also known paratransgenesis. An essential step in developing paratransgenic stable colonization adult flies and their progeny with recombinant bacteria, expressing trypanocidal effector molecules tissues where parasite resides. In...
The African trypanosome Trypanosoma brucei, which persists within the bloodstream of mammalian host, has evolved potent mechanisms for immune evasion. Specifically, antigenic variation variant-specific surface glycoprotein (VSG) and a highly active endocytosis recycling coat efficiently delay killing mediated by anti-VSG antibodies. Consequently, conventional VSG-specific intact immunoglobulins are non-trypanocidal in absence complement. In sharp contrast, monovalent antigen-binding...
Background In order to promote infection, the blood-borne parasite Trypanosoma brucei releases factors that upregulate arginase expression and activity in myeloid cells. Methodology/Principal findings By screening a cDNA library of T. with an antibody neutralizing arginase-inducing released factors, we identified Kinesin Heavy Chain isoform, termed TbKHC1, as responsible for this effect. Following interaction mouse cells, natural or recombinant TbKHC1 triggered SIGN-R1 receptor-dependent...
Three new chemical series (bicyclic nitroimidazoles, aminopyrazoles and oxaboroles) were selected by Drugs for Neglected Diseases initiative as potential drug leads leishmaniasis. Pharmacodynamics studies included both in vitro vivo efficacy, cross-resistance profiling against the current antileishmanial reference drugs evaluation of their cidal activity potential. Efficacy laboratory strains Leishmania infantum (MHOM/MA(BE)/67/ITMAP263) L. donovani (MHOM/ET/67/L82) was evaluated on...
Streptococcus pneumoniae is the leading cause of bacterial pneumonia. Infection linked to high morbidity and mortality rates antibiotic resistance within this pathogen on rise. Therefore, there a need for novel antimicrobial therapies. To lower time costs drug discovery process, alternative in vivo models should be considered. As such, Galleria mellonella larvae can great value. The larval immunity consisting several types haemocytes remarkably similar human innate immune system....
Abstract Given the discontinuation of various first-line drugs for visceral leishmaniasis (VL), large-scale in vivo drug screening, establishment a relapse model rodents, immunophenotyping, and transcriptomics were combined to study persistent infections therapeutic failure. Double bioluminescent/fluorescent Leishmania infantum L. donovani reporter lines enabled identification long-term hematopoietic stem cells (LT-HSC) as niche bone marrow with remarkably high parasite burdens, feature...
New drugs for visceral leishmaniasis that are safe, low cost, and adapted to the field urgently required. Despite concerted efforts over last several years, number of new chemical entities suitable clinical development treatment Leishmania remains low. Here, we describe discovery preclinical DNDI-6174, an inhibitor cytochrome bc 1 complex activity originated from a phenotypically identified pyrrolopyrimidine series. This compound fulfills all target candidate profile criteria required...
Abstract Several quinoline derivatives incorporating arylnitro and aminochalcone moieties were synthesized evaluated in vitro against a broad panel of trypanosomatid protozoan parasites responsible for sleeping sickness ( Trypanosoma brucei rhodesiense ), nagana Chagas disease cruzi leishmaniasis Leishmania infantum ). the compounds demonstrated significant antiprotozoal activity. Specifically, 2c , 2d 4i displayed submicromolar activity T. b. with half‐maximal effective concentration (EC 50...
Abstract Kinetoplastids are a group of flagellated protozoans including medically important parasites the genus Trypanosoma and Leishmania . The corresponding diseases have afflicted humans for centuries. In an effort to combat kinetoplastid infections, set 21 chalcones was synthesized evaluated their in vitro anti-protozoal efficacy against brucei , rhodesiense cruzi infantum To ensure safety, these compounds underwent selectivity evaluation by assessing toxicity human lung fibroblast cell...