9 results on '"Caljon, Guy"'
Search Results
2. Evaluation of a pan-Leishmania SL RNA qPCR assay for parasite detection in laboratory-reared and field-collected sand flies and reservoir hosts
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Pareyn, Myrthe, Hendrickx, Rik, Girma, Nigatu, Hendrickx, Sarah, Van Bockstal, Lieselotte, Van Houtte, Natalie, Shibru, Simon, Maes, Louis, Leirs, Herwig, and Caljon, Guy
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- 2020
- Full Text
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3. Phenotypic adaptations of Leishmania donovani to recurrent miltefosine exposure and impact on sand fly infection
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Hendrickx, Sarah, Van Bockstal, Lieselotte, Bulté, Dimitri, Mondelaers, Annelies, Aslan, Hamide, Rivas, Luis, Maes, Louis, and Caljon, Guy
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- 2020
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4. Comparative genomic analysis of six Glossina genomes, vectors of African trypanosomes
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Attardo, Geoffrey M., Abd-Alla, Adly M. M., Acosta-Serrano, Alvaro, Allen, James E., Bateta, Rosemary, Benoit, Joshua B., Bourtzis, Kostas, Caers, Jelle, Caljon, Guy, Christensen, Mikkel B., Farrow, David W., Friedrich, Markus, Hua-Van, Aurélie, Jennings, Emily C., Larkin, Denis M., Lawson, Daniel, Lehane, Michael J., Lenis, Vasileios P., Lowy-Gallego, Ernesto, Macharia, Rosaline W., Malacrida, Anna R., Marco, Heather G., Masiga, Daniel, Maslen, Gareth L., Matetovici, Irina, Meisel, Richard P., Meki, Irene, Michalkova, Veronika, Miller, Wolfgang J., Minx, Patrick, Mireji, Paul O., Ometto, Lino, Parker, Andrew G., Rio, Rita, Rose, Clair, Rosendale, Andrew J., Rota-Stabelli, Omar, Savini, Grazia, Schoofs, Liliane, Scolari, Francesca, Swain, Martin T., Takáč, Peter, Tomlinson, Chad, Tsiamis, George, Van Den Abbeele, Jan, Vigneron, Aurelien, Wang, Jingwen, Warren, Wesley C., Waterhouse, Robert M., Weirauch, Matthew T., Weiss, Brian L., Wilson, Richard K., Zhao, Xin, and Aksoy, Serap
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- 2019
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5. Phenotypic adaptations of Leishmania donovani to recurrent miltefosine exposure and impact on sand fly infection
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Research Foundation - Flanders, University of Antwerp, Hendrickx, Sarah, Van Bockstal, Lieselotte, Bulté, Dimitri, Mondelaers, Annelies, Aslan, Hamide, Rivas, Luis, Maes, Louis, Caljon, Guy, Research Foundation - Flanders, University of Antwerp, Hendrickx, Sarah, Van Bockstal, Lieselotte, Bulté, Dimitri, Mondelaers, Annelies, Aslan, Hamide, Rivas, Luis, Maes, Louis, and Caljon, Guy
- Abstract
[Background]: Since the introduction of miltefosine (MIL) as first-line therapy in the kala-azar elimination programme in the Indian subcontinent, treatment failure rates have been increasing. Since parasite infectivity and virulence may become altered upon treatment relapse, this laboratory study assessed the phenotypic effects of repeated in vitro and in vivo MIL exposure., [Methods]: Syngeneic Leishmania donovani lines either or not exposed to MIL were compared for drug susceptibility, rate of promastigote multiplication and metacyclogenesis, macrophage infectivity and behaviour in the sand fly vector, Lutzomyia longipalpis., [Results]: Promastigotes of both in vitro and in vivo MIL-selected strains displayed a slightly reduced drug susceptibility that was associated with a reduced MIL-accumulation linked to a lower copy number (disomic state) of chromosome 13 harboring the miltefosine transporter (LdMT) gene. In vitro selected promastigotes showed a lower rate of metacyclogenesis whereas the in vivo derived promastigotes displayed a moderately increased growth rate. Repeated MIL exposure did neither influence the parasite load nor metacyclogenesis in the sand fly vector., [Conclusions]: Recurrent in vitro and in vivo MIL exposure evokes a number of very subtle phenotypic and genotypic changes which could make promastigotes less susceptible to MIL without attaining full resistance. These changes did not significantly impact on infection in the sand fly vector.
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- 2020
6. Respiratory syncytial virus (RSV) entry is inhibited by serine protease inhibitor AEBSF when present during an early stage of infection.
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Van der Gucht, Winke, Leemans, Annelies, De Schryver, Marjorie, Heykers, Annick, Caljon, Guy, Maes, Louis, Cos, Paul, and Delputte, Peter L.
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Background: Host proteases have been shown to play important roles in many viral activities such as entry, uncoating, viral protein production and disease induction. Therefore, these cellular proteases are putative targets for the development of antivirals that inhibit their activity. Host proteases have been described to play essential roles in Ebola, HCV, HIV and influenza, such that specific protease inhibitors are able to reduce infection. RSV utilizes a host protease in its replication cycle but its potential as antiviral target is unknown. Therefore, we evaluated the effect of protease inhibitors on RSV infection. Methods: To measure the sensitivity of RSV infection to protease inhibitors, cells were infected with RSV and incubated for 18 h in the presence or absence of the inhibitors. Cells were fixed, stained and studied using fluorescence microscopy. Results: Several protease inhibitors, representing different classes of proteases (AEBSF, Pepstatin A, E-64, TPCK, PMSF and aprotinin), were tested for inhibitory effects on an RSV A2 infection of HEp-2 cells. Different treatment durations, ranging from 1 h prior to inoculation and continuing for 18 h during the assay, were evaluated. Of all the inhibitors tested, AEBSF and TPCK significantly decreased RSV infection. To ascertain that the observed effect of AEBSF was not a specific feature related to HEp-2 cells, A549 and BEAS-2B cells were also used. Similar to HEp-2, an almost complete block in the number of RSV infected cells after 18 h of incubation was observed and the effect was dose-dependent. To gain insight into the mechanism of this inhibition, AEBSF treatment was applied during different phases of an infection cycle (pre-, peri- and post-inoculation treatment). The results from these experiments indicate that AEBSF is mainly active during the early entry phase of RSV. The inhibitory effect was also observed with other RSV isolates A1998/3–2 and A2000/3–4, suggesting that this is a general feature of RSV. Conclusion: RSV infection can be inhibited by broad serine protease inhibitors, AEBSF and TPCK. We confirmed that AEBSF inhibition is independent of the cell line used or RSV strain. The time point at which treatment with the inhibitor was most potent, was found to coincide with the expected moment of entry of the virion with the host cell. [ABSTRACT FROM AUTHOR]
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- 2017
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7. Tsetse fly tolerance to T. brucei infection: transcriptome analysis of trypanosome-associated changes in the tsetse fly salivary gland.
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Matetovici, Irina, Caljon, Guy, and Van Den Abbeele, Jan
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FLY behavior , *PARASITES , *METACYCLOPINA , *SALIVARY gland diseases , *MEDICAL microbiology - Abstract
Background: For their transmission, African trypanosomes rely on their blood feeding insect vector, the tsetse fly (Glossina sp.). The ingested Trypanosoma brucei parasites have to overcome a series of barriers in the tsetse fly alimentary tract to finally develop into the infective metacyclic forms in the salivary glands that are transmitted to a mammalian host by the tsetse bite. The parasite population in the salivary gland is dense with a significant number of trypanosomes tightly attached to the epithelial cells. Our current knowledge on the impact of the infection on the salivary gland functioning is very limited. Therefore, this study aimed to gain a deeper insight into the global gene expression changes in the salivary glands of Glossina morsitans morsitans in response to an infection with the T. brucei parasite. A detailed whole transcriptome comparison of midgut-infected tsetse with and without a mature salivary gland infection was performed to study the impact of a trypanosome infection on different aspects of the salivary gland functioning and the mechanisms that are induced in this tissue to tolerate the infection i.e. to control the negative impact of the parasite presence. Moreover, a transcriptome comparison with age-matched uninfected flies was done to see whether gene expression in the salivary glands is already affected by a trypanosome infection in the tsetse midgut. Results: By a RNA-sequencing (RNA-seq) approach we compared the whole transcriptomes of flies with a T. brucei salivary gland/midgut infection versus flies with only a midgut infection or versus non-infected flies, all with the same age and feeding history. More than 7500 salivary gland transcripts were detected from which a core group of 1214 differentially expressed genes (768 up- and 446 down-regulated) were shared between the two transcriptional comparisons. Gene Ontology enrichment analysis and detailed gene expression comparisons showed a diverse impact at the gene transcript level. Increased expression was observed for transcripts encoding for proteins involved in immunity (like several genes of the Imd-signaling pathway, serine proteases, serpins and thioestercontaining proteins), detoxification of reactive species, cell death, cytoskeleton organization, cell junction and repair. Decreased expression was observed for transcripts encoding the major secreted proteins such as 5'-nucleotidases, adenosine deaminases and the nucleic acid binding proteins Tsals. Moreover, expression of some gene categories in the salivary glands were found to be already affected by a trypanosome midgut infection, before the parasite reaches the salivary glands. Conclusions: This study reveals that the T. brucei population in the tsetse salivary gland has a negative impact on its functioning and on the integrity of the gland epithelium. Our RNA-seq data suggest induction of a strong local tissue response in order to control the epithelial cell damage, the ROS intoxication of the cellular environment and the parasite infection, resulting in the fly tolerance to the infection. The modified expression of some gene categories in the tsetse salivary glands by a trypanosome infection at the midgut level indicate a putative anticipatory response in the salivary glands, before the parasite reaches this tissue. [ABSTRACT FROM AUTHOR]
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- 2016
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8. Delivery of a functional anti-trypanosome Nanobody in different tsetse fly tissues via a bacterial symbiont, Sodalis glossinidius.
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De Vooght, Linda, Caljon, Guy, De Ridder, Karin, and Den Abbeele, Jan Van
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TSETSE-flies , *RECOMBINANT proteins , *GRAM-negative bacteria , *PROTEIN expression , *VECTOR-pathogen relationships - Abstract
Background Sodalis glossinidius, a vertically transmitted microbial symbiont of the tsetse fly, is currently considered as a potential delivery system for anti-trypanosomal components that reduce or eliminate the capability of the tsetse fly host to transmit parasitic trypanosomes, an approach also known as paratransgenesis. An essential step in developing paratransgenic tsetse is the stable colonization of adult flies and their progeny with recombinant Sodalis bacteria, expressing trypanocidal effector molecules in tissues where the parasite resides. Results In this study, Sodalis was tested for its ability to deliver functional anti-trypanosome nanobodies (Nbs) in Glossina morsitans morsitans. We characterized the in vitro and in vivo stability of recombinant Sodalis (recSodalis) expressing a potent trypanolytic nanobody, i.e. Nb_An46. We show that recSodalis is competitive with WT Sodalis in in vivo conditions and that tsetse flies transiently cleared of their endogenous WT Sodalis population can be successfully repopulated with recSodalis at high densities. In addition, vertical transmission to the offspring was observed. Finally, we demonstrated that recSodalis expressed significant levels (ng range) of functional Nb_An46 in different tsetse fly tissues, including the midgut where an important developmental stage of the trypanosome parasite occurs. Conclusions We demonstrated the proof-of-concept that the Sodalis symbiont can be genetically engineered to express and release significant amounts of functional anti-trypanosome Nbs in different tissues of the tsetse fly. The application of this innovative concept of using pathogen-targeting nanobodies delivered by insect symbiotic bacteria could be extended to other vector-pathogen systems. [ABSTRACT FROM AUTHOR]
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- 2014
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9. Expression and extracellular release of a functional anti-trypanosome Nanobody® in Sodalis glossinidius, a bacterial symbiont of the tsetse fly.
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De Vooght L, Caljon G, Stijlemans B, De Baetselier P, Coosemans M, and Van den Abbeele J
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- Animals, Antibodies, Protozoan genetics, Antibodies, Protozoan immunology, Gene Expression, Glycoproteins immunology, Periplasm metabolism, Protein Sorting Signals genetics, Protozoan Proteins immunology, Recombinant Fusion Proteins biosynthesis, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins immunology, Trypanosoma brucei brucei metabolism, Antibodies, Protozoan biosynthesis, Enterobacteriaceae metabolism, Symbiosis, Tsetse Flies microbiology
- Abstract
Background: Sodalis glossinidius, a gram-negative bacterial endosymbiont of the tsetse fly, has been proposed as a potential in vivo drug delivery vehicle to control trypanosome parasite development in the fly, an approach known as paratransgenesis. Despite this interest of S. glossinidius as a paratransgenic platform organism in tsetse flies, few potential effector molecules have been identified so far and to date none of these molecules have been successfully expressed in this bacterium., Results: In this study, S. glossinidius was transformed to express a single domain antibody, (Nanobody®) Nb_An33, that efficiently targets conserved cryptic epitopes of the variant surface glycoprotein (VSG) of the parasite Trypanosoma brucei. Next, we analyzed the capability of two predicted secretion signals to direct the extracellular delivery of significant levels of active Nb_An33. We show that the pelB leader peptide was successful in directing the export of fully functional Nb_An33 to the periplasm of S. glossinidius resulting in significant levels of extracellular release. Finally, S. glossinidius expressing pelBNb_An33 exhibited no significant reduction in terms of fitness, determined by in vitro growth kinetics, compared to the wild-type strain., Conclusions: These data are the first demonstration of the expression and extracellular release of functional trypanosome-interfering Nanobodies® in S. glossinidius. Furthermore, Sodalis strains that efficiently released the effector protein were not affected in their growth, suggesting that they may be competitive with endogenous microbiota in the midgut environment of the tsetse fly. Collectively, these data reinforce the notion for the potential of S. glossinidius to be developed into a paratransgenic platform organism.
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- 2012
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