The Experts below are selected from a list of 17187 Experts worldwide ranked by ideXlab platform
Yagya D Sharma - One of the best experts on this subject based on the ideXlab platform.
-
basigin interacts with plasmodium vivax tryptophan rich antigen pvtrag38 as a second erythrocyte receptor to promote Parasite growth
Journal of Biological Chemistry, 2017Co-Authors: Sumit Rathore, Sheena Dass, Divya Kandari, Inderjeet Kaur, Mayank Gupta, Yagya D SharmaAbstract:Elucidating the molecular mechanisms of the Host-Parasite Interaction during red cell invasion by Plasmodium is important for developing newer antimalarial therapeutics. Recently, we have characterized a Plasmodium vivax tryptophan-rich antigen PvTRAg38, which is expressed by its merozoites, binds to Host erythrocytes, and interferes with Parasite growth. Interaction of this Parasite ligand with the Host erythrocyte occurs through its two regions present at amino acid positions 167-178 (P2) and 197-208 (P4). Each region recognizes its own erythrocyte receptor. Previously, we identified band 3 as the chymotrypsin-sensitive erythrocyte receptor for the P4 region, but the other receptor, binding to P2 region, remained unknown. Here, we have identified basigin as the second erythrocyte receptor for PvTRAg38, which is resistant to chymotrypsin. The specificity of Interaction between PvTRAg38 and basigin was confirmed by direct Interaction where basigin was specifically recognized by P2 and not by the P4 region of this Parasite ligand. Interaction between P2 and basigin is stabilized through multiple amino acid residues, but Gly-171 and Leu-175 of P2 were more critical. These two amino acids were also critical for Parasite growth. Synthetic peptides P2 and P4 of PvTRAg38 interfered with the Parasite growth independently but had an additive effect if combined together indicating involvement of both the receptors during red cell invasion. In conclusion, PvTRAg38 binds to two erythrocyte receptors basigin and band 3 through P2 and P4 regions, respectively, to facilitate Parasite growth. This advancement in our knowledge on molecular mechanisms of Host-Parasite Interaction can be exploited to develop therapeutics against P. vivax malaria.
-
Interaction of plasmodium vivax tryptophan rich antigen pvtrag38 with band 3 on human erythrocyte surface facilitates Parasite growth
Journal of Biological Chemistry, 2015Co-Authors: Mohd Shoeb Alam, Vandana Choudhary, Mohammad Zeeshan, Rupesh K Tyagi, Sumit Rathore, Yagya D SharmaAbstract:Plasmodium tryptophan-rich proteins are involved in Host-Parasite Interaction and thus potential drug/vaccine targets. Recently, we have described several P. vivax tryptophan-rich antigens (PvTRAgs), including merozoite expressed PvTRAg38, from this noncultivable human malaria Parasite. PvTRAg38 is highly immunogenic in humans and binds to Host erythrocytes, and this binding is inhibited by the patient sera. This binding is also affected if Host erythrocytes were pretreated with chymotrypsin. Here, Band 3 has been identified as the chymotrypsin-sensitive erythrocyte receptor for this Parasite protein. Interaction of PvTRAg38 with Band 3 has been mapped to its three different ectodomains (loops 1, 3, and 6) exposed at the surface of the erythrocyte. The binding region of PvTRAg38 to Band3 has been mapped to its sequence, KWVQWKNDKIRSWLSSEW, present at amino acid positions 197-214. The recombinant PvTRAg38 was able to inhibit the Parasite growth in in vitro Plasmodium falciparum culture probably by competing with the ligand(s) of this heterologous Parasite for the erythrocyte Band 3 receptor. In conclusion, the Host-Parasite Interaction at the molecular level is much more complicated than known so far and should be considered during the development of anti-malarial therapeutics.
Sumit Rathore - One of the best experts on this subject based on the ideXlab platform.
-
basigin interacts with plasmodium vivax tryptophan rich antigen pvtrag38 as a second erythrocyte receptor to promote Parasite growth
Journal of Biological Chemistry, 2017Co-Authors: Sumit Rathore, Sheena Dass, Divya Kandari, Inderjeet Kaur, Mayank Gupta, Yagya D SharmaAbstract:Elucidating the molecular mechanisms of the Host-Parasite Interaction during red cell invasion by Plasmodium is important for developing newer antimalarial therapeutics. Recently, we have characterized a Plasmodium vivax tryptophan-rich antigen PvTRAg38, which is expressed by its merozoites, binds to Host erythrocytes, and interferes with Parasite growth. Interaction of this Parasite ligand with the Host erythrocyte occurs through its two regions present at amino acid positions 167-178 (P2) and 197-208 (P4). Each region recognizes its own erythrocyte receptor. Previously, we identified band 3 as the chymotrypsin-sensitive erythrocyte receptor for the P4 region, but the other receptor, binding to P2 region, remained unknown. Here, we have identified basigin as the second erythrocyte receptor for PvTRAg38, which is resistant to chymotrypsin. The specificity of Interaction between PvTRAg38 and basigin was confirmed by direct Interaction where basigin was specifically recognized by P2 and not by the P4 region of this Parasite ligand. Interaction between P2 and basigin is stabilized through multiple amino acid residues, but Gly-171 and Leu-175 of P2 were more critical. These two amino acids were also critical for Parasite growth. Synthetic peptides P2 and P4 of PvTRAg38 interfered with the Parasite growth independently but had an additive effect if combined together indicating involvement of both the receptors during red cell invasion. In conclusion, PvTRAg38 binds to two erythrocyte receptors basigin and band 3 through P2 and P4 regions, respectively, to facilitate Parasite growth. This advancement in our knowledge on molecular mechanisms of Host-Parasite Interaction can be exploited to develop therapeutics against P. vivax malaria.
-
Interaction of plasmodium vivax tryptophan rich antigen pvtrag38 with band 3 on human erythrocyte surface facilitates Parasite growth
Journal of Biological Chemistry, 2015Co-Authors: Mohd Shoeb Alam, Vandana Choudhary, Mohammad Zeeshan, Rupesh K Tyagi, Sumit Rathore, Yagya D SharmaAbstract:Plasmodium tryptophan-rich proteins are involved in Host-Parasite Interaction and thus potential drug/vaccine targets. Recently, we have described several P. vivax tryptophan-rich antigens (PvTRAgs), including merozoite expressed PvTRAg38, from this noncultivable human malaria Parasite. PvTRAg38 is highly immunogenic in humans and binds to Host erythrocytes, and this binding is inhibited by the patient sera. This binding is also affected if Host erythrocytes were pretreated with chymotrypsin. Here, Band 3 has been identified as the chymotrypsin-sensitive erythrocyte receptor for this Parasite protein. Interaction of PvTRAg38 with Band 3 has been mapped to its three different ectodomains (loops 1, 3, and 6) exposed at the surface of the erythrocyte. The binding region of PvTRAg38 to Band3 has been mapped to its sequence, KWVQWKNDKIRSWLSSEW, present at amino acid positions 197-214. The recombinant PvTRAg38 was able to inhibit the Parasite growth in in vitro Plasmodium falciparum culture probably by competing with the ligand(s) of this heterologous Parasite for the erythrocyte Band 3 receptor. In conclusion, the Host-Parasite Interaction at the molecular level is much more complicated than known so far and should be considered during the development of anti-malarial therapeutics.
Klaus Brehm - One of the best experts on this subject based on the ideXlab platform.
-
The role of fibroblast growth factor signalling in Echinococcus multilocularis development and Host-Parasite Interaction
PLoS Neglected Tropical Diseases, 2019Co-Authors: Sabine Förster, Uriel Koziol, Tina Schäfer, Raphael Duvoisin, Katia Cailliau, Mathieu Vanderstraete, Colette Dissous, Klaus BrehmAbstract:BACKGROUND: Alveolar echinococcosis (AE) is a lethal zoonosis caused by the metacestode larva of the tapeworm Echinococcus multilocularis. The infection is characterized by tumour-like growth of the metacestode within the Host liver, leading to extensive fibrosis and organ-failure. The molecular mechanisms of Parasite organ tropism towards the liver and influences of liver cytokines and hormones on Parasite development are little studied to date. METHODOLOGY/PRINCIPAL FINDINGS: We show that the E. multilocularis larval stage expresses three members of the fibroblast growth factor (FGF) receptor family with homology to human FGF receptors. Using the Xenopus expression system we demonstrate that all three Echinococcus FGF receptors are activated in response to human acidic and basic FGF, which are present in the liver. In all three cases, activation could be prevented by addition of the tyrosine kinase (TK) inhibitor BIBF 1120, which is used to treat human cancer. At physiological concentrations, acidic and basic FGF significantly stimulated the formation of metacestode vesicles from Parasite stem cells in vitro and supported metacestode growth. Furthermore, the Parasite's mitogen activated protein kinase signalling system was stimulated upon addition of human FGF. The survival of metacestode vesicles and Parasite stem cells were drastically affected in vitro in the presence of BIBF 1120. CONCLUSIONS/SIGNIFICANCE: Our data indicate that mammalian FGF, which is present in the liver and upregulated during fibrosis, supports the establishment of the Echinococcus metacestode during AE by acting on an evolutionarily conserved Parasite FGF signalling system. These data are valuable for understanding molecular mechanisms of organ tropism and Host-Parasite Interaction in AE. Furthermore, our data indicate that the Parasite's FGF signalling systems are promising targets for the development of novel drugs against AE.
-
the role of fibroblast growth factor signalling in echinococcus multilocularis development and Host Parasite Interaction
bioRxiv, 2018Co-Authors: Sabine Förster, Uriel Koziol, Tina Schäfer, Raphael Duvoisin, Katia Cailliau, Mathieu Vanderstraete, Colette Dissous, Klaus BrehmAbstract:Abstract Background Alveolar echinococcosis (AE) is a lethal zoonosis caused by the metacestode larva of the tapeworm Echinococcus multilocularis. The infection is characterized by tumour-like growth of the metacestode within the Host liver, leading to extensive fibrosis and organ-failure. The molecular mechanisms of Parasite organ tropism towards the liver and influences of liver cytokines and hormones on Parasite development are little studied to date. Methodology/Principal findings We show that the E. multilocularis larval stage expresses three members of the fibroblast growth factor (FGF) receptor family with homology to human FGF receptors. Using the Xenopus expression system we demonstrate that all three Echinococcus FGF receptors are activated in response to human acidic and basic FGF, which are present in the liver. In all three cases, activation could be prevented by addition of the tyrosine kinase inhibitor BIBF 1120, which is used to treat human cancer. At physiological concentrations, acidic and basic FGF significantly stimulated the formation of metacestode vesicles from Parasite stem cells in vitro and supported metacestode growth. Furthermore, the Parasite’s mitogen activated protein kinase signalling system was stimulated upon addition of human FGF. The survival of metacestode vesicles and Parasite stem cells were drastically affected in vitro in the presence of BIBF 1120. Conclusions/Significance Our data indicate that mammalian FGF, which is present in the liver and upregulated during fibrosis, supports the establishment of the Echinococcus metacestode during AE by acting on an evolutionarily conserved Parasite FGF signalling system. These data are valuable for understanding molecular mechanisms of organ tropism and Host-Parasite Interaction in AE. Furthermore, our data indicate that the Parasite’s FGF signalling systems are promising targets for the development of novel drugs against AE. Author summary To ensure proper communication between their different cell populations, animals rely on secreted hormones and cytokines that act on receptors of target cells. Most of the respective cytokines, such as FGFs, evolved over 500 million years ago and are present in similar form in all animals, including parasitic worms. The authors of this study show that the metacestode larva of the tapeworm E. multilocularis, which grows like a malignant tumor within the Host liver, expresses molecules with homology to FGF receptors from mammals. The authors show that human FGF, which is abundantly present in the liver, stimulates metacestode development and that all Parasite FGF receptors are activated by human FGF, despite 500 million years of evolutionary distance between both systems. This indicates that cells of the Echinococcus metacestode can directly communicate with cells of the mammalian Host using evolutionarily conserved signaling molecules. This mode of Host-pathogen Interaction is unique for helminths and does not occur between mammals and single-celled pathogens such as protozoans or bacteria. The authors finally demonstrate that BIBF 1120, a drug used to treat human cancer, targets the Echinococcus FGF receptors and leads to Parasite death. This opens new ways for the development of anti-parasitic drugs.
-
the role of evolutionarily conserved signalling systems in echinococcus multilocularis development and Host Parasite Interaction
Medical Microbiology and Immunology, 2010Co-Authors: Klaus BrehmAbstract:Alveolar echinococcosis, one of the most serious and life-threatening zoonoses in the world, is caused by the metacestode larval stage of the fox-tapeworm Echinococcus multilocularis. Mostly due to its accessibility to in vitro cultivation, this Parasite has recently evolved into an experimental model system to study larval cestode development and associated Host-Parasite Interaction mechanisms. Respective advances include the establishment of axenic in vitro cultivation systems for Parasite larvae as well as culture systems by which the early development of metacestode vesicles from totipotent Parasite stem cells can be reconstituted under controlled laboratory conditions. A series of evolutionarily conserved signalling molecules of the insulin, epidermal growth factor and transforming growth factor-beta pathways that are able to functionally interact with corresponding Host cytokines have been described in E. multilocularis and most likely play a crucial role in Parasite development within the liver of the intermediate Host. Furthermore, a whole genome sequencing project has been initiated by which a comprehensive picture on E. multilocularis cell-cell communication systems will be available in due time, including information on Parasite cytokines that are secreted towards Host tissue and thus might affect the immune response. In this article, an overview of our current picture on Echinococcus signalling systems will be given, and the potential to exploit these pathways as targets for anti-parasitic chemotherapy will be discussed.
-
echinococcus multilocularis as an experimental model in stem cell research and molecular Host Parasite Interaction
Parasitology, 2010Co-Authors: Klaus BrehmAbstract:Totipotent somatic stem cells (neoblasts) are key players in the biology of flatworms and account for their amazing regenerative capability and developmental plasticity. During recent years, considerable progress has been made in elucidating molecular features of neoblasts from free-living flatworms, whereas their role in parasitic species has so far merely been addressed by descriptive studies. Very recently, however, significant advances have been made in the in vitro culture of neoblasts from the cestode Echinococcus multilocularis. The isolated cells proved capable of generating mature metacestode vesicles under laboratory conditions in a manner that closely resembles the oncosphere-metacestode transition during natural infections. Using the established neoblast cultivation protocols, combined with targeted manipulation of Echinococcus genes by RNA-interference, several fundamental questions of Host-dependent Parasite development can now be addressed. Here, I give an overview of current cultivation techniques for E. multilocularis neoblasts and present experimental approaches to study their function. Furthermore, I introduce the E. multilocularis genome sequencing project that is presently in an advanced stage. The combined input of data from the E. multilocularis sequencing project, stem cell cultivation, and recently initiated attempts to genetically manipulate Echinococcus will provide an ideal platform for hypothesis-driven research into cestode development in the next years.
Ulrike Kemmerling - One of the best experts on this subject based on the ideXlab platform.
-
Host Parasite Interaction changes in human placental gene expression induced by trypanosoma cruzi
Parasites & Vectors, 2018Co-Authors: Christian Castillo, Ileana Carrillo, Gabriela Libisch, Natalia Juiz, Alejandro Schijman, Carlos Robello, Ulrike KemmerlingAbstract:Chagas disease is caused by Trypanosoma cruzi, a Parasite endemic to Latin America. Most infections occur in children by vector or congenital transmission. Trypanosoma cruzi establishes a complexity of specific molecular Parasite-Host cell Interactions to invade the Host. However, most studies have been mainly focused on the Interaction between the Parasite and different cell types, but not on the infection and invasion on a tissue level. During congenital transmission, T. cruzi must cross the placental barrier, composed of epithelial and connective tissues, in order to infect the developing fetus. Here we aimed to study the global changes of transcriptome in the placental tissue after a T. cruzi challenge. Strong changes in gene expression profiling were found in the different experimental conditions, involving the reprogramming of gene expression in genes involved in the innate immune response. Trypanosoma cruzi induces strong changes in genes involved in a wide range of pathways, especially those involved in immune response against infections.
-
Host-Parasite Interaction: changes in human placental gene expression induced by Trypanosoma cruzi
BMC, 2018Co-Authors: Christian Castillo, Ileana Carrillo, Gabriela Libisch, Natalia Juiz, Alejandro Schijman, Carlos Robello, Ulrike KemmerlingAbstract:Abstract Background Chagas disease is caused by Trypanosoma cruzi, a Parasite endemic to Latin America. Most infections occur in children by vector or congenital transmission. Trypanosoma cruzi establishes a complexity of specific molecular Parasite-Host cell Interactions to invade the Host. However, most studies have been mainly focused on the Interaction between the Parasite and different cell types, but not on the infection and invasion on a tissue level. During congenital transmission, T. cruzi must cross the placental barrier, composed of epithelial and connective tissues, in order to infect the developing fetus. Here we aimed to study the global changes of transcriptome in the placental tissue after a T. cruzi challenge. Results Strong changes in gene expression profiling were found in the different experimental conditions, involving the reprogramming of gene expression in genes involved in the innate immune response. Conclusions Trypanosoma cruzi induces strong changes in genes involved in a wide range of pathways, especially those involved in immune response against infections
Mohd Shoeb Alam - One of the best experts on this subject based on the ideXlab platform.
-
Interaction of plasmodium vivax tryptophan rich antigen pvtrag38 with band 3 on human erythrocyte surface facilitates Parasite growth
Journal of Biological Chemistry, 2015Co-Authors: Mohd Shoeb Alam, Vandana Choudhary, Mohammad Zeeshan, Rupesh K Tyagi, Sumit Rathore, Yagya D SharmaAbstract:Plasmodium tryptophan-rich proteins are involved in Host-Parasite Interaction and thus potential drug/vaccine targets. Recently, we have described several P. vivax tryptophan-rich antigens (PvTRAgs), including merozoite expressed PvTRAg38, from this noncultivable human malaria Parasite. PvTRAg38 is highly immunogenic in humans and binds to Host erythrocytes, and this binding is inhibited by the patient sera. This binding is also affected if Host erythrocytes were pretreated with chymotrypsin. Here, Band 3 has been identified as the chymotrypsin-sensitive erythrocyte receptor for this Parasite protein. Interaction of PvTRAg38 with Band 3 has been mapped to its three different ectodomains (loops 1, 3, and 6) exposed at the surface of the erythrocyte. The binding region of PvTRAg38 to Band3 has been mapped to its sequence, KWVQWKNDKIRSWLSSEW, present at amino acid positions 197-214. The recombinant PvTRAg38 was able to inhibit the Parasite growth in in vitro Plasmodium falciparum culture probably by competing with the ligand(s) of this heterologous Parasite for the erythrocyte Band 3 receptor. In conclusion, the Host-Parasite Interaction at the molecular level is much more complicated than known so far and should be considered during the development of anti-malarial therapeutics.