The Experts below are selected from a list of 99 Experts worldwide ranked by ideXlab platform
Rafael Toledo - One of the best experts on this subject based on the ideXlab platform.
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definitive host influences the proteomic profile of excretory secretory products of the trematode echinostoma caproni
Parasites & Vectors, 2016Co-Authors: Alba Cortes, Javier Sotillo, Carla Munozantoli, Maria Trelis, Guillermo J Esteban, Rafael ToledoAbstract:Echinostoma caproni is an intestinal trematode extensively used as experimental model for the study of factors that determine the course of intestinal helminth infections, since this markedly depends on the host species. Although the host-dependent mechanisms for either chronic establishment or early parasite rejection have been broadly studied, little is known regarding the parasite response against different host environments. To identify host-dependent differentially expressed proteins, a comparative proteomic analysis of the excretory/secretory products released from E. caproni adults, isolated from hosts displaying different compatibility with this trematode, was performed. A total of 19 differential protein spots were identified (14 overexpressed in mice and 5 overexpressed in rats). The establishment of chronic infections in mice is mainly associated with the overexpression by adult worms of antioxidant and detoxifying enzymes (e.g. glutathione S-transferase, Hydroxyacylglutathione Hydrolase, thiopurine S-transferase, etc.) and metabolic enzymes like enolase, leucine aminopeptidase or malate dehydrogenase. However, the overexpression of cathepsin L and the structural protein actin observed in worms isolated from rats seems not to be effective for the colonization of the intestinal mucosa of this host. The observed differences suggest that protein expression and/or release is modulated by the local environment generated inside the host and provide useful insights in regards to the resistance mechanisms developed by parasites to ensure their long-term survival.
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Definitive host influences the proteomic profile of excretory/secretory products of the trematode Echinostoma caproni
Parasites & Vectors, 2016Co-Authors: Alba Cortes, Javier Sotillo, Maria Trelis, Carla Muñoz-antolí, J. Guillermo Esteban, Rafael ToledoAbstract:Background Echinostoma caproni is an intestinal trematode extensively used as experimental model for the study of factors that determine the course of intestinal helminth infections, since this markedly depends on the host species. Although the host-dependent mechanisms for either chronic establishment or early parasite rejection have been broadly studied, little is known regarding the parasite response against different host environments. Methods To identify host-dependent differentially expressed proteins, a comparative proteomic analysis of the excretory/secretory products released from E. caproni adults, isolated from hosts displaying different compatibility with this trematode, was performed. Results A total of 19 differential protein spots were identified (14 overexpressed in mice and 5 overexpressed in rats). The establishment of chronic infections in mice is mainly associated with the overexpression by adult worms of antioxidant and detoxifying enzymes (e.g. glutathione S-transferase, Hydroxyacylglutathione Hydrolase, thiopurine S-transferase, etc.) and metabolic enzymes like enolase, leucine aminopeptidase or malate dehydrogenase. However, the overexpression of cathepsin L and the structural protein actin observed in worms isolated from rats seems not to be effective for the colonization of the intestinal mucosa of this host. Conclusions The observed differences suggest that protein expression and/or release is modulated by the local environment generated inside the host and provide useful insights in regards to the resistance mechanisms developed by parasites to ensure their long-term survival.
Javier Sotillo - One of the best experts on this subject based on the ideXlab platform.
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definitive host influences the proteomic profile of excretory secretory products of the trematode echinostoma caproni
Parasites & Vectors, 2016Co-Authors: Alba Cortes, Javier Sotillo, Carla Munozantoli, Maria Trelis, Guillermo J Esteban, Rafael ToledoAbstract:Echinostoma caproni is an intestinal trematode extensively used as experimental model for the study of factors that determine the course of intestinal helminth infections, since this markedly depends on the host species. Although the host-dependent mechanisms for either chronic establishment or early parasite rejection have been broadly studied, little is known regarding the parasite response against different host environments. To identify host-dependent differentially expressed proteins, a comparative proteomic analysis of the excretory/secretory products released from E. caproni adults, isolated from hosts displaying different compatibility with this trematode, was performed. A total of 19 differential protein spots were identified (14 overexpressed in mice and 5 overexpressed in rats). The establishment of chronic infections in mice is mainly associated with the overexpression by adult worms of antioxidant and detoxifying enzymes (e.g. glutathione S-transferase, Hydroxyacylglutathione Hydrolase, thiopurine S-transferase, etc.) and metabolic enzymes like enolase, leucine aminopeptidase or malate dehydrogenase. However, the overexpression of cathepsin L and the structural protein actin observed in worms isolated from rats seems not to be effective for the colonization of the intestinal mucosa of this host. The observed differences suggest that protein expression and/or release is modulated by the local environment generated inside the host and provide useful insights in regards to the resistance mechanisms developed by parasites to ensure their long-term survival.
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Definitive host influences the proteomic profile of excretory/secretory products of the trematode Echinostoma caproni
Parasites & Vectors, 2016Co-Authors: Alba Cortes, Javier Sotillo, Maria Trelis, Carla Muñoz-antolí, J. Guillermo Esteban, Rafael ToledoAbstract:Background Echinostoma caproni is an intestinal trematode extensively used as experimental model for the study of factors that determine the course of intestinal helminth infections, since this markedly depends on the host species. Although the host-dependent mechanisms for either chronic establishment or early parasite rejection have been broadly studied, little is known regarding the parasite response against different host environments. Methods To identify host-dependent differentially expressed proteins, a comparative proteomic analysis of the excretory/secretory products released from E. caproni adults, isolated from hosts displaying different compatibility with this trematode, was performed. Results A total of 19 differential protein spots were identified (14 overexpressed in mice and 5 overexpressed in rats). The establishment of chronic infections in mice is mainly associated with the overexpression by adult worms of antioxidant and detoxifying enzymes (e.g. glutathione S-transferase, Hydroxyacylglutathione Hydrolase, thiopurine S-transferase, etc.) and metabolic enzymes like enolase, leucine aminopeptidase or malate dehydrogenase. However, the overexpression of cathepsin L and the structural protein actin observed in worms isolated from rats seems not to be effective for the colonization of the intestinal mucosa of this host. Conclusions The observed differences suggest that protein expression and/or release is modulated by the local environment generated inside the host and provide useful insights in regards to the resistance mechanisms developed by parasites to ensure their long-term survival.
Alba Cortes - One of the best experts on this subject based on the ideXlab platform.
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definitive host influences the proteomic profile of excretory secretory products of the trematode echinostoma caproni
Parasites & Vectors, 2016Co-Authors: Alba Cortes, Javier Sotillo, Carla Munozantoli, Maria Trelis, Guillermo J Esteban, Rafael ToledoAbstract:Echinostoma caproni is an intestinal trematode extensively used as experimental model for the study of factors that determine the course of intestinal helminth infections, since this markedly depends on the host species. Although the host-dependent mechanisms for either chronic establishment or early parasite rejection have been broadly studied, little is known regarding the parasite response against different host environments. To identify host-dependent differentially expressed proteins, a comparative proteomic analysis of the excretory/secretory products released from E. caproni adults, isolated from hosts displaying different compatibility with this trematode, was performed. A total of 19 differential protein spots were identified (14 overexpressed in mice and 5 overexpressed in rats). The establishment of chronic infections in mice is mainly associated with the overexpression by adult worms of antioxidant and detoxifying enzymes (e.g. glutathione S-transferase, Hydroxyacylglutathione Hydrolase, thiopurine S-transferase, etc.) and metabolic enzymes like enolase, leucine aminopeptidase or malate dehydrogenase. However, the overexpression of cathepsin L and the structural protein actin observed in worms isolated from rats seems not to be effective for the colonization of the intestinal mucosa of this host. The observed differences suggest that protein expression and/or release is modulated by the local environment generated inside the host and provide useful insights in regards to the resistance mechanisms developed by parasites to ensure their long-term survival.
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Definitive host influences the proteomic profile of excretory/secretory products of the trematode Echinostoma caproni
Parasites & Vectors, 2016Co-Authors: Alba Cortes, Javier Sotillo, Maria Trelis, Carla Muñoz-antolí, J. Guillermo Esteban, Rafael ToledoAbstract:Background Echinostoma caproni is an intestinal trematode extensively used as experimental model for the study of factors that determine the course of intestinal helminth infections, since this markedly depends on the host species. Although the host-dependent mechanisms for either chronic establishment or early parasite rejection have been broadly studied, little is known regarding the parasite response against different host environments. Methods To identify host-dependent differentially expressed proteins, a comparative proteomic analysis of the excretory/secretory products released from E. caproni adults, isolated from hosts displaying different compatibility with this trematode, was performed. Results A total of 19 differential protein spots were identified (14 overexpressed in mice and 5 overexpressed in rats). The establishment of chronic infections in mice is mainly associated with the overexpression by adult worms of antioxidant and detoxifying enzymes (e.g. glutathione S-transferase, Hydroxyacylglutathione Hydrolase, thiopurine S-transferase, etc.) and metabolic enzymes like enolase, leucine aminopeptidase or malate dehydrogenase. However, the overexpression of cathepsin L and the structural protein actin observed in worms isolated from rats seems not to be effective for the colonization of the intestinal mucosa of this host. Conclusions The observed differences suggest that protein expression and/or release is modulated by the local environment generated inside the host and provide useful insights in regards to the resistance mechanisms developed by parasites to ensure their long-term survival.
Florian L. Muller - One of the best experts on this subject based on the ideXlab platform.
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Antimicrobial Prodrug Activation by the Staphylococcal Glyoxalase GloB.
ACS infectious diseases, 2020Co-Authors: Marwa O. Mikati, Justin J. Miller, Damon M. Osbourn, Yasaman Barekatain, Naomi Ghebremichael, Ishaan T. Shah, Carey-ann D. Burnham, Kenneth M. Heidel, Victoria C. Yan, Florian L. MullerAbstract:With the rising prevalence of multidrug resistance, there is an urgent need to develop novel antibiotics. Many putative antibiotics demonstrate promising in vitro potency but fail in vivo due to poor drug-like qualities (e.g., serum half-life, oral absorption, solubility, and toxicity). These drug-like properties can be modified through the addition of chemical protecting groups, creating "prodrugs" that are activated prior to target inhibition. Lipophilic prodrugging techniques, including the attachment of a pivaloyloxymethyl group, have garnered attention for their ability to increase cellular permeability by masking charged residues and the relative ease of the chemical prodrugging process. Unfortunately, pivaloyloxymethyl prodrugs are rapidly activated by human sera, rendering any membrane permeability qualities absent during clinical treatment. Identification of the bacterial prodrug activation pathway(s) will allow for the development of host-stable and microbe-targeted prodrug therapies. Here, we use two zoonotic staphylococcal species, Staphylococcus schleiferi and S. pseudintermedius, to establish the mechanism of carboxy ester prodrug activation. Using a forward genetic screen, we identify a conserved locus in both species encoding the enzyme Hydroxyacylglutathione Hydrolase (GloB), whose loss-of-function confers resistance to carboxy ester prodrugs. We enzymatically characterize GloB and demonstrate that it is a functional glyoxalase II enzyme, which has the capacity to activate carboxy ester prodrugs. As GloB homologues are both widespread and diverse in sequence, our findings suggest that GloB may be a useful mechanism for developing species- or genus-level prodrug targeting strategies.
Marwa O. Mikati - One of the best experts on this subject based on the ideXlab platform.
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Antimicrobial Prodrug Activation by the Staphylococcal Glyoxalase GloB.
ACS infectious diseases, 2020Co-Authors: Marwa O. Mikati, Justin J. Miller, Damon M. Osbourn, Yasaman Barekatain, Naomi Ghebremichael, Ishaan T. Shah, Carey-ann D. Burnham, Kenneth M. Heidel, Victoria C. Yan, Florian L. MullerAbstract:With the rising prevalence of multidrug resistance, there is an urgent need to develop novel antibiotics. Many putative antibiotics demonstrate promising in vitro potency but fail in vivo due to poor drug-like qualities (e.g., serum half-life, oral absorption, solubility, and toxicity). These drug-like properties can be modified through the addition of chemical protecting groups, creating "prodrugs" that are activated prior to target inhibition. Lipophilic prodrugging techniques, including the attachment of a pivaloyloxymethyl group, have garnered attention for their ability to increase cellular permeability by masking charged residues and the relative ease of the chemical prodrugging process. Unfortunately, pivaloyloxymethyl prodrugs are rapidly activated by human sera, rendering any membrane permeability qualities absent during clinical treatment. Identification of the bacterial prodrug activation pathway(s) will allow for the development of host-stable and microbe-targeted prodrug therapies. Here, we use two zoonotic staphylococcal species, Staphylococcus schleiferi and S. pseudintermedius, to establish the mechanism of carboxy ester prodrug activation. Using a forward genetic screen, we identify a conserved locus in both species encoding the enzyme Hydroxyacylglutathione Hydrolase (GloB), whose loss-of-function confers resistance to carboxy ester prodrugs. We enzymatically characterize GloB and demonstrate that it is a functional glyoxalase II enzyme, which has the capacity to activate carboxy ester prodrugs. As GloB homologues are both widespread and diverse in sequence, our findings suggest that GloB may be a useful mechanism for developing species- or genus-level prodrug targeting strategies.
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Antimicrobial prodrug activation by the staphylococcal glyoxalase GloB
2020Co-Authors: Marwa O. Mikati, Justin J. Miller, Damon M. Osbourn, Naomi Ghebremichael, Ishaan T. Shah, Carey-ann D. Burnham, Kenneth M. Heidel, Victoria C. Yan, F. L. Mueller, Cynthia S. DowdAbstract:ABSTRACT With the rising prevalence of multidrug-resistance, there is an urgent need to develop novel antibiotics. Many putative antibiotics demonstrate promising in vitro potency but fail in vivo due to poor drug-like qualities (e.g. serum half-life, oral absorption, solubility, toxicity). These drug-like properties can be modified through the addition of chemical protecting groups, creating “prodrugs” that are activated prior to target inhibition. Lipophilic prodrugging techniques, including the attachment of a pivaloyloxymethyl group, have garnered attention for their ability to increase cellular permeability by masking charged residues and the relative ease of the chemical prodrugging process. Unfortunately, pivaloyloxymethyl prodrugs are rapidly activated by human sera, rendering any membrane permeability qualities absent during clinical treatment. Identification of the bacterial prodrug activation pathway(s) will allow for the development of host-stable and microbe-targeted prodrug therapies. Here, we use two zoonotic staphylococcal species, S. schleiferi and S. pseudintermedius, to establish the mechanism of carboxy ester prodrug activation. Using a forward genetic screen, we identify a conserved locus in both species encoding the enzyme Hydroxyacylglutathione Hydrolase (GloB), whose loss-of-function confers resistance to carboxy ester prodrugs. We enzymatically characterize GloB and demonstrate that it is a functional glyoxalase II enzyme, which has the capacity to activate carboxy ester prodrugs. As GloB homologs are both widespread and diverse in sequence, our findings suggest that GloB may be a useful mechanism for developing species-or genus-level prodrug targeting strategies.
