Invasion of <Emphasis Type="Italic">Trypanosoma cruzi</Emphasis> into host cells is impaired by <Emphasis Type="Italic">N</Emphasis>-propionylmannosamine and other <Emphasis Type="Italic">N</Emphasis>-acylmannosamines |
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Authors: | Thorsten Lieke Daniel Gröbe Véronique Blanchard Detlef Grunow Rudolf Tauber Martin Zimmermann-Kordmann Thomas Jacobs Werner Reutter |
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Institution: | 1.Bernhard-Nocht-Institut für Tropenmedizin,Hamburg,Germany;2.Institut für Laboratoriumsmedizin und Pathobiochemie,Charité-Universit?tsmedizin,Berlin,Germany;3.Institut für Biochemie und Molekularbiologie,Charité-Universit?tsmedizin Berlin (Freie Universit?t Berlin),Berlin-Dahlem,Germany |
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Abstract: | The etiologic agent of Chagas’ disease, Trypanosoma cruzi, is widely distributed in South America, affecting millions of people with thousands of deaths every year. Adherence of the
infectious trypomastigote to host cells is mediated by sialic acid. T. cruzi cannot synthesize sialic acids on their own but cleave them from the host cells and link them to glycans on the surface of
the parasites using the trans-sialidase, a GPI-anchored enzyme. The infectivity of the protozoan parasites strongly depends
on the activity of this enzyme. In this report, we investigated whether the transfer of sialic acids from the host to the
parasites can be attenuated using novel sialic acid precursors. The cell line 86-HG-39 was infected with T. cruzi and treated with defined N-acylmannosamine analogues bearing an elongated N-acyl side-chain. By treatment of these cells the number of T.cruzi infected cell was reduced up to 60%. We also showed that the activity of the bacterial sialidase C was reduced with N-glycan
substrates with elongated N-acyl side chains of the terminal sialic acids. The affinity of this sialidase decreased with the length of the N-acyl side-chain. The data presented suggest that N-acyl modified sialic acid precursors can change the transfer of sialic acids leading to modification of infection. Since
the chemotherapy of this disease is inefficient and afflicted by side effects, the need of effective drugs is lasting. These
findings propose a new path to prevent the dissemination of T. cruzi in the human hosts. These compounds or further modified analogues might be a basis for the search of new agents against Chagas’
disease. |
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