Nagana

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Reto Brun - One of the best experts on this subject based on the ideXlab platform.

  • A NOVEL ANTIMICROBIAL PEPTIDE WITH ANTIPARASITIC ACTIVITY IN THE BLOOD-SUCKING INSECT STOMOXYS CALCITRANS*
    2020
    Co-Authors: Nathalie Boulanger, Reto Brun, R J L Munks, Joanne V Hamilton, Michael J. Lehane, Philippe Bulet
    Abstract:

    The gut epithelium is an essential interface in insects that transmit parasites. We investigated the role that local innate immunity might have on vector compe- tence, taking Stomoxys calcitrans as a model. S. calci- trans is sympatric with tsetse flies, feeds on many of the same vertebrate hosts, and is thus regularly exposed to the trypanosomes that cause African sleeping sickness and Nagana. Despite this, S. calcitrans is not a cyclical vector of these trypanosomes. Trypanosomes develop exclusively in the lumen of digestive organs, and so ep- ithelial immune mechanisms, and in particular antimi- crobial peptides (AMPs), may be the prime determinants of the fate of an infection. To investigate why S. calci- trans is not a cyclical vector of trypanosomes, we have looked in its midgut for AMPs with trypanolytic activity. We have identified a new AMP of 42 amino acids, which we named stomoxyn, constitutively expressed and se- creted exclusively in the anterior midgut of S. calci- trans. It displays an amphipathic helical structure and exhibits a broad activity spectrum affecting the growth of microorganisms. Interestingly, this AMP exhibits trypanolytic activity to Trypanosoma brucei rhod- esiense. We argue that stomoxyn may help to explain why S. calcitrans is not a vector of trypanosomes caus- ing African sleeping sickness and Nagana.

  • Isothermal microcalorimetry - A quantitative method to monitor Trypanosoma congolense growth and growth inhibition by trypanocidal drugs in real time.
    International Journal for Parasitology-Drugs and Drug Resistance, 2018
    Co-Authors: M. Gysin, Kirsten Gillingwater, Reto Brun, Olivier Braissant, Pascal Mäser, Tanja Wenzler
    Abstract:

    Abstract Trypanosoma congolense is a protozoan parasite that is transmitted by tsetse flies, causing African Animal Trypanosomiasis, also known as Nagana, in sub-Saharan Africa. Nagana is a fatal disease of livestock that causes severe economic losses. Two drugs are available, diminazene and isometamidium, yet successful treatment is jeopardized by drug resistant T. congolense . Isothermal microcalorimetry is a highly sensitive tool that can be used to study growth of the extracellular T. congolense parasites or to study parasite growth inhibition after the addition of antitrypanosomal drugs. Time of drug action and time to kill can be quantified in a simple way by real time heat flow measurements. We established a robust protocol for the microcalorimetric studies of T. congolense and developed mathematical computations in R to calculate different parameters related to growth and the kinetics of drug action. We demonstrate the feasibility and benefit of the method exemplary with the two standard drugs, diminazene aceturate and isometamidium chloride. The method and the mathematical approach can be translated to study other pathogenic or non-pathogenic cells if they are metabolically active and grow under axenic conditions.

  • In Vitro, Ex Vivo, and In Vivo Activities of Diamidines against Trypanosoma congolense and Trypanosoma vivax
    Antimicrobial Agents and Chemotherapy, 2017
    Co-Authors: Kirsten Gillingwater, Christina Kunz, Christiane Braghiroli, David W. Boykin, Richard R. Tidwell, Reto Brun
    Abstract:

    African animal trypanosomosis (AAT) is caused by the tsetse fly-transmitted protozoans Trypanosoma congolense and T. vivax and leads to huge agricultural losses throughout sub-Saharan Africa. Three drugs are available to treat Nagana in cattle (diminazene diaceturate, homidium chloride, and isometamidium chloride). With increasing reports of drug-resistant populations, new molecules should be investigated as potential candidates to combat Nagana. Dicationic compounds have been demonstrated to have excellent efficacy against different kinetoplastid parasites. This study therefore evaluated the activities of 37 diamidines, using in vitro and ex vivo drug sensitivity assays. The 50% inhibitory concentrations obtained ranged from 0.007 to 0.562 μg/ml for T. congolense and from 0.019 to 0.607 μg/ml for T. vivax On the basis of these promising results, 33 of these diamidines were further examined using in vivo mouse models of infection. Minimal curative doses of 1.25 mg/kg of body weight for both T. congolense- and T. vivax-infected mice were seen when the diamidines were administered intraperitoneally (i.p.) over 4 consecutive days. From these observations, 15 of these 33 diamidines were then further tested in vivo, using a single bolus dose for administration. The total cure of mice infected with T. congolense and T. vivax was seen with single i.p. doses of 5 and 2.5 mg/kg, respectively. This study identified a selection of diamidines which could be considered lead compounds for the treatment of Nagana.

  • epithelial innate immunity a novel antimicrobial peptide with antiparasitic activity in the blood sucking insect stomoxys calcitrans
    Journal of Biological Chemistry, 2002
    Co-Authors: Nathalie Boulanger, Reto Brun, M. J. Lehane, R J L Munks, Joanne V Hamilton, Francoise Vovelle, Philippe Bulet
    Abstract:

    Abstract The gut epithelium is an essential interface in insects that transmit parasites. We investigated the role that local innate immunity might have on vector competence, taking Stomoxys calcitrans as a model. S. calcitrans is sympatric with tsetse flies, feeds on many of the same vertebrate hosts, and is thus regularly exposed to the trypanosomes that cause African sleeping sickness and Nagana. Despite this, S. calcitrans is not a cyclical vector of these trypanosomes. Trypanosomes develop exclusively in the lumen of digestive organs, and so epithelial immune mechanisms, and in particular antimicrobial peptides (AMPs), may be the prime determinants of the fate of an infection. To investigate why S. calcitrans is not a cyclical vector of trypanosomes, we have looked in its midgut for AMPs with trypanolytic activity. We have identified a new AMP of 42 amino acids, which we named stomoxyn, constitutively expressed and secreted exclusively in the anterior midgut of S. calcitrans. It displays an amphipathic helical structure and exhibits a broad activity spectrum affecting the growth of microorganisms. Interestingly, this AMP exhibits trypanolytic activity to Trypanosoma brucei rhodesiense. We argue that stomoxyn may help to explain why S. calcitrans is not a vector of trypanosomes causing African sleeping sickness and Nagana.

Philippe Bulet - One of the best experts on this subject based on the ideXlab platform.

  • A NOVEL ANTIMICROBIAL PEPTIDE WITH ANTIPARASITIC ACTIVITY IN THE BLOOD-SUCKING INSECT STOMOXYS CALCITRANS*
    2020
    Co-Authors: Nathalie Boulanger, Reto Brun, R J L Munks, Joanne V Hamilton, Michael J. Lehane, Philippe Bulet
    Abstract:

    The gut epithelium is an essential interface in insects that transmit parasites. We investigated the role that local innate immunity might have on vector compe- tence, taking Stomoxys calcitrans as a model. S. calci- trans is sympatric with tsetse flies, feeds on many of the same vertebrate hosts, and is thus regularly exposed to the trypanosomes that cause African sleeping sickness and Nagana. Despite this, S. calcitrans is not a cyclical vector of these trypanosomes. Trypanosomes develop exclusively in the lumen of digestive organs, and so ep- ithelial immune mechanisms, and in particular antimi- crobial peptides (AMPs), may be the prime determinants of the fate of an infection. To investigate why S. calci- trans is not a cyclical vector of trypanosomes, we have looked in its midgut for AMPs with trypanolytic activity. We have identified a new AMP of 42 amino acids, which we named stomoxyn, constitutively expressed and se- creted exclusively in the anterior midgut of S. calci- trans. It displays an amphipathic helical structure and exhibits a broad activity spectrum affecting the growth of microorganisms. Interestingly, this AMP exhibits trypanolytic activity to Trypanosoma brucei rhod- esiense. We argue that stomoxyn may help to explain why S. calcitrans is not a vector of trypanosomes caus- ing African sleeping sickness and Nagana.

  • epithelial innate immunity a novel antimicrobial peptide with antiparasitic activity in the blood sucking insect stomoxys calcitrans
    Journal of Biological Chemistry, 2002
    Co-Authors: Nathalie Boulanger, Reto Brun, M. J. Lehane, R J L Munks, Joanne V Hamilton, Francoise Vovelle, Philippe Bulet
    Abstract:

    Abstract The gut epithelium is an essential interface in insects that transmit parasites. We investigated the role that local innate immunity might have on vector competence, taking Stomoxys calcitrans as a model. S. calcitrans is sympatric with tsetse flies, feeds on many of the same vertebrate hosts, and is thus regularly exposed to the trypanosomes that cause African sleeping sickness and Nagana. Despite this, S. calcitrans is not a cyclical vector of these trypanosomes. Trypanosomes develop exclusively in the lumen of digestive organs, and so epithelial immune mechanisms, and in particular antimicrobial peptides (AMPs), may be the prime determinants of the fate of an infection. To investigate why S. calcitrans is not a cyclical vector of trypanosomes, we have looked in its midgut for AMPs with trypanolytic activity. We have identified a new AMP of 42 amino acids, which we named stomoxyn, constitutively expressed and secreted exclusively in the anterior midgut of S. calcitrans. It displays an amphipathic helical structure and exhibits a broad activity spectrum affecting the growth of microorganisms. Interestingly, this AMP exhibits trypanolytic activity to Trypanosoma brucei rhodesiense. We argue that stomoxyn may help to explain why S. calcitrans is not a vector of trypanosomes causing African sleeping sickness and Nagana.

Nathalie Boulanger - One of the best experts on this subject based on the ideXlab platform.

  • A NOVEL ANTIMICROBIAL PEPTIDE WITH ANTIPARASITIC ACTIVITY IN THE BLOOD-SUCKING INSECT STOMOXYS CALCITRANS*
    2020
    Co-Authors: Nathalie Boulanger, Reto Brun, R J L Munks, Joanne V Hamilton, Michael J. Lehane, Philippe Bulet
    Abstract:

    The gut epithelium is an essential interface in insects that transmit parasites. We investigated the role that local innate immunity might have on vector compe- tence, taking Stomoxys calcitrans as a model. S. calci- trans is sympatric with tsetse flies, feeds on many of the same vertebrate hosts, and is thus regularly exposed to the trypanosomes that cause African sleeping sickness and Nagana. Despite this, S. calcitrans is not a cyclical vector of these trypanosomes. Trypanosomes develop exclusively in the lumen of digestive organs, and so ep- ithelial immune mechanisms, and in particular antimi- crobial peptides (AMPs), may be the prime determinants of the fate of an infection. To investigate why S. calci- trans is not a cyclical vector of trypanosomes, we have looked in its midgut for AMPs with trypanolytic activity. We have identified a new AMP of 42 amino acids, which we named stomoxyn, constitutively expressed and se- creted exclusively in the anterior midgut of S. calci- trans. It displays an amphipathic helical structure and exhibits a broad activity spectrum affecting the growth of microorganisms. Interestingly, this AMP exhibits trypanolytic activity to Trypanosoma brucei rhod- esiense. We argue that stomoxyn may help to explain why S. calcitrans is not a vector of trypanosomes caus- ing African sleeping sickness and Nagana.

  • epithelial innate immunity a novel antimicrobial peptide with antiparasitic activity in the blood sucking insect stomoxys calcitrans
    Journal of Biological Chemistry, 2002
    Co-Authors: Nathalie Boulanger, Reto Brun, M. J. Lehane, R J L Munks, Joanne V Hamilton, Francoise Vovelle, Philippe Bulet
    Abstract:

    Abstract The gut epithelium is an essential interface in insects that transmit parasites. We investigated the role that local innate immunity might have on vector competence, taking Stomoxys calcitrans as a model. S. calcitrans is sympatric with tsetse flies, feeds on many of the same vertebrate hosts, and is thus regularly exposed to the trypanosomes that cause African sleeping sickness and Nagana. Despite this, S. calcitrans is not a cyclical vector of these trypanosomes. Trypanosomes develop exclusively in the lumen of digestive organs, and so epithelial immune mechanisms, and in particular antimicrobial peptides (AMPs), may be the prime determinants of the fate of an infection. To investigate why S. calcitrans is not a cyclical vector of trypanosomes, we have looked in its midgut for AMPs with trypanolytic activity. We have identified a new AMP of 42 amino acids, which we named stomoxyn, constitutively expressed and secreted exclusively in the anterior midgut of S. calcitrans. It displays an amphipathic helical structure and exhibits a broad activity spectrum affecting the growth of microorganisms. Interestingly, this AMP exhibits trypanolytic activity to Trypanosoma brucei rhodesiense. We argue that stomoxyn may help to explain why S. calcitrans is not a vector of trypanosomes causing African sleeping sickness and Nagana.

Joanne V Hamilton - One of the best experts on this subject based on the ideXlab platform.

  • A NOVEL ANTIMICROBIAL PEPTIDE WITH ANTIPARASITIC ACTIVITY IN THE BLOOD-SUCKING INSECT STOMOXYS CALCITRANS*
    2020
    Co-Authors: Nathalie Boulanger, Reto Brun, R J L Munks, Joanne V Hamilton, Michael J. Lehane, Philippe Bulet
    Abstract:

    The gut epithelium is an essential interface in insects that transmit parasites. We investigated the role that local innate immunity might have on vector compe- tence, taking Stomoxys calcitrans as a model. S. calci- trans is sympatric with tsetse flies, feeds on many of the same vertebrate hosts, and is thus regularly exposed to the trypanosomes that cause African sleeping sickness and Nagana. Despite this, S. calcitrans is not a cyclical vector of these trypanosomes. Trypanosomes develop exclusively in the lumen of digestive organs, and so ep- ithelial immune mechanisms, and in particular antimi- crobial peptides (AMPs), may be the prime determinants of the fate of an infection. To investigate why S. calci- trans is not a cyclical vector of trypanosomes, we have looked in its midgut for AMPs with trypanolytic activity. We have identified a new AMP of 42 amino acids, which we named stomoxyn, constitutively expressed and se- creted exclusively in the anterior midgut of S. calci- trans. It displays an amphipathic helical structure and exhibits a broad activity spectrum affecting the growth of microorganisms. Interestingly, this AMP exhibits trypanolytic activity to Trypanosoma brucei rhod- esiense. We argue that stomoxyn may help to explain why S. calcitrans is not a vector of trypanosomes caus- ing African sleeping sickness and Nagana.

  • epithelial innate immunity a novel antimicrobial peptide with antiparasitic activity in the blood sucking insect stomoxys calcitrans
    Journal of Biological Chemistry, 2002
    Co-Authors: Nathalie Boulanger, Reto Brun, M. J. Lehane, R J L Munks, Joanne V Hamilton, Francoise Vovelle, Philippe Bulet
    Abstract:

    Abstract The gut epithelium is an essential interface in insects that transmit parasites. We investigated the role that local innate immunity might have on vector competence, taking Stomoxys calcitrans as a model. S. calcitrans is sympatric with tsetse flies, feeds on many of the same vertebrate hosts, and is thus regularly exposed to the trypanosomes that cause African sleeping sickness and Nagana. Despite this, S. calcitrans is not a cyclical vector of these trypanosomes. Trypanosomes develop exclusively in the lumen of digestive organs, and so epithelial immune mechanisms, and in particular antimicrobial peptides (AMPs), may be the prime determinants of the fate of an infection. To investigate why S. calcitrans is not a cyclical vector of trypanosomes, we have looked in its midgut for AMPs with trypanolytic activity. We have identified a new AMP of 42 amino acids, which we named stomoxyn, constitutively expressed and secreted exclusively in the anterior midgut of S. calcitrans. It displays an amphipathic helical structure and exhibits a broad activity spectrum affecting the growth of microorganisms. Interestingly, this AMP exhibits trypanolytic activity to Trypanosoma brucei rhodesiense. We argue that stomoxyn may help to explain why S. calcitrans is not a vector of trypanosomes causing African sleeping sickness and Nagana.

R J L Munks - One of the best experts on this subject based on the ideXlab platform.

  • A NOVEL ANTIMICROBIAL PEPTIDE WITH ANTIPARASITIC ACTIVITY IN THE BLOOD-SUCKING INSECT STOMOXYS CALCITRANS*
    2020
    Co-Authors: Nathalie Boulanger, Reto Brun, R J L Munks, Joanne V Hamilton, Michael J. Lehane, Philippe Bulet
    Abstract:

    The gut epithelium is an essential interface in insects that transmit parasites. We investigated the role that local innate immunity might have on vector compe- tence, taking Stomoxys calcitrans as a model. S. calci- trans is sympatric with tsetse flies, feeds on many of the same vertebrate hosts, and is thus regularly exposed to the trypanosomes that cause African sleeping sickness and Nagana. Despite this, S. calcitrans is not a cyclical vector of these trypanosomes. Trypanosomes develop exclusively in the lumen of digestive organs, and so ep- ithelial immune mechanisms, and in particular antimi- crobial peptides (AMPs), may be the prime determinants of the fate of an infection. To investigate why S. calci- trans is not a cyclical vector of trypanosomes, we have looked in its midgut for AMPs with trypanolytic activity. We have identified a new AMP of 42 amino acids, which we named stomoxyn, constitutively expressed and se- creted exclusively in the anterior midgut of S. calci- trans. It displays an amphipathic helical structure and exhibits a broad activity spectrum affecting the growth of microorganisms. Interestingly, this AMP exhibits trypanolytic activity to Trypanosoma brucei rhod- esiense. We argue that stomoxyn may help to explain why S. calcitrans is not a vector of trypanosomes caus- ing African sleeping sickness and Nagana.

  • epithelial innate immunity a novel antimicrobial peptide with antiparasitic activity in the blood sucking insect stomoxys calcitrans
    Journal of Biological Chemistry, 2002
    Co-Authors: Nathalie Boulanger, Reto Brun, M. J. Lehane, R J L Munks, Joanne V Hamilton, Francoise Vovelle, Philippe Bulet
    Abstract:

    Abstract The gut epithelium is an essential interface in insects that transmit parasites. We investigated the role that local innate immunity might have on vector competence, taking Stomoxys calcitrans as a model. S. calcitrans is sympatric with tsetse flies, feeds on many of the same vertebrate hosts, and is thus regularly exposed to the trypanosomes that cause African sleeping sickness and Nagana. Despite this, S. calcitrans is not a cyclical vector of these trypanosomes. Trypanosomes develop exclusively in the lumen of digestive organs, and so epithelial immune mechanisms, and in particular antimicrobial peptides (AMPs), may be the prime determinants of the fate of an infection. To investigate why S. calcitrans is not a cyclical vector of trypanosomes, we have looked in its midgut for AMPs with trypanolytic activity. We have identified a new AMP of 42 amino acids, which we named stomoxyn, constitutively expressed and secreted exclusively in the anterior midgut of S. calcitrans. It displays an amphipathic helical structure and exhibits a broad activity spectrum affecting the growth of microorganisms. Interestingly, this AMP exhibits trypanolytic activity to Trypanosoma brucei rhodesiense. We argue that stomoxyn may help to explain why S. calcitrans is not a vector of trypanosomes causing African sleeping sickness and Nagana.