Invasion of Trypanosoma cruzi into host cells is impaired by N-propionylmannosamine and other N-acylmannosamines.
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.
Bernhard-Nocht-Institut für Tropenmedizin, Bernhard-Nocht-Straße 74, 20359, Hamburg, Germany.
Thorsten
T
Lieke
Daniel
D
Gröbe
Véronique
V
Blanchard
Detlef
D
Grunow
Rudolf
R
Tauber
Martin
M
Zimmermann-Kordmann
Thomas
T
Jacobs
Werner
W
Reutter
D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003412:Cricetulus; D006595:Hexosamines / Q000494:pharmacology*; D006790:Host-Parasite Interactions / Q000187:drug effects*; D006801:Humans; D014349:Trypanosoma cruzi / Q000502:physiology*
D006595:Hexosamines; C415828:N-propionylmannosamine
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