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APOLs with low pH dependence can kill all African trypanosomes

The primate-specific serum protein apolipoprotein L1 (APOL1) is the only secreted member of a family of cell death promoting proteins1–4. APOL1 kills the bloodstream parasite Trypanosoma brucei brucei, but not the human sleeping sickness agents T.b. rhodesiense and T.b. gambiense3. We considered the...

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Autores principales: Fontaine, Frédéric, Lecordier, Laurence, Vanwalleghem, Gilles, Uzureau, Pierrick, Van Reet, Nick, Fontaine, Martina, Tebabi, Patricia, Vanhollebeke, Benoit, Büscher, Philippe, Pérez-Morga, David, Pays, Etienne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660622/
https://www.ncbi.nlm.nih.gov/pubmed/28924146
http://dx.doi.org/10.1038/s41564-017-0034-1
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author Fontaine, Frédéric
Lecordier, Laurence
Vanwalleghem, Gilles
Uzureau, Pierrick
Van Reet, Nick
Fontaine, Martina
Tebabi, Patricia
Vanhollebeke, Benoit
Büscher, Philippe
Pérez-Morga, David
Pays, Etienne
author_facet Fontaine, Frédéric
Lecordier, Laurence
Vanwalleghem, Gilles
Uzureau, Pierrick
Van Reet, Nick
Fontaine, Martina
Tebabi, Patricia
Vanhollebeke, Benoit
Büscher, Philippe
Pérez-Morga, David
Pays, Etienne
author_sort Fontaine, Frédéric
collection PubMed
description The primate-specific serum protein apolipoprotein L1 (APOL1) is the only secreted member of a family of cell death promoting proteins1–4. APOL1 kills the bloodstream parasite Trypanosoma brucei brucei, but not the human sleeping sickness agents T.b. rhodesiense and T.b. gambiense3. We considered the possibility that intracellular members of the APOL1 family, against which extracellular trypanosomes could not have evolved resistance, could kill pathogenic T. brucei subspecies. Here we show that recombinant APOL3 (rAPOL3) kills all African trypanosomes including T.b. rhodesiense, T.b. gambiense and the animal pathogens T. evansi, T. congolense and T. vivax. In contrast, rAPOL3 did not kill more distant trypanosomes such as T. theileri or T. cruzi. This trypanolytic potential was partially shared by rAPOL1 from Papio papio (rPpAPOL1). The differential killing ability between rAPOL3 and rAPOL1 was associated with distinct dependence on acidic pH for activity. Due to both instability and toxicity when injected into mice rAPOL3 cannot be used for treatment of infection, but an experimental rPpAPOL1 mutant inspired by APOL3 exhibited enhanced trypanolytic activity in vitro and ability to completely inhibit T.b. gambiense infection in mice. We conclude that pH dependence influences the trypanolytic potential of rAPOLs.
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spelling pubmed-56606222018-03-18 APOLs with low pH dependence can kill all African trypanosomes Fontaine, Frédéric Lecordier, Laurence Vanwalleghem, Gilles Uzureau, Pierrick Van Reet, Nick Fontaine, Martina Tebabi, Patricia Vanhollebeke, Benoit Büscher, Philippe Pérez-Morga, David Pays, Etienne Nat Microbiol Article The primate-specific serum protein apolipoprotein L1 (APOL1) is the only secreted member of a family of cell death promoting proteins1–4. APOL1 kills the bloodstream parasite Trypanosoma brucei brucei, but not the human sleeping sickness agents T.b. rhodesiense and T.b. gambiense3. We considered the possibility that intracellular members of the APOL1 family, against which extracellular trypanosomes could not have evolved resistance, could kill pathogenic T. brucei subspecies. Here we show that recombinant APOL3 (rAPOL3) kills all African trypanosomes including T.b. rhodesiense, T.b. gambiense and the animal pathogens T. evansi, T. congolense and T. vivax. In contrast, rAPOL3 did not kill more distant trypanosomes such as T. theileri or T. cruzi. This trypanolytic potential was partially shared by rAPOL1 from Papio papio (rPpAPOL1). The differential killing ability between rAPOL3 and rAPOL1 was associated with distinct dependence on acidic pH for activity. Due to both instability and toxicity when injected into mice rAPOL3 cannot be used for treatment of infection, but an experimental rPpAPOL1 mutant inspired by APOL3 exhibited enhanced trypanolytic activity in vitro and ability to completely inhibit T.b. gambiense infection in mice. We conclude that pH dependence influences the trypanolytic potential of rAPOLs. 2017-09-18 2017-11 /pmc/articles/PMC5660622/ /pubmed/28924146 http://dx.doi.org/10.1038/s41564-017-0034-1 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Fontaine, Frédéric
Lecordier, Laurence
Vanwalleghem, Gilles
Uzureau, Pierrick
Van Reet, Nick
Fontaine, Martina
Tebabi, Patricia
Vanhollebeke, Benoit
Büscher, Philippe
Pérez-Morga, David
Pays, Etienne
APOLs with low pH dependence can kill all African trypanosomes
title APOLs with low pH dependence can kill all African trypanosomes
title_full APOLs with low pH dependence can kill all African trypanosomes
title_fullStr APOLs with low pH dependence can kill all African trypanosomes
title_full_unstemmed APOLs with low pH dependence can kill all African trypanosomes
title_short APOLs with low pH dependence can kill all African trypanosomes
title_sort apols with low ph dependence can kill all african trypanosomes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660622/
https://www.ncbi.nlm.nih.gov/pubmed/28924146
http://dx.doi.org/10.1038/s41564-017-0034-1
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