Differential toxicity of ricin and diphtheria toxin for bloodstream forms of Trypanosoma brucei.

Abstract:

:The cytotoxicity of ricin and diphtheria toxin was studied in culture-adapted bloodstream forms of Trypanosoma brucei. Although ricin is endocytosed at a rate comparable to that of other internalized macromolecules, it is nontoxic to bloodstream-form trypanosomes. The resistance lies partly in low susceptibility of the targeted ribosomes: T. brucei cell-free protein biosynthesis is only partially inhibited by ricin A chain. In addition, ricin is degraded before it reaches the ribosomes, as the toxin is delivered to lysosomes. In contrast, diphtheria toxin shows similar cytotoxicities for bloodstream-form trypanosomes and mouse myeloma cells. Both trypanosome and myeloma cells are more than 1000-fold less sensitive to the action of the toxin than most other mammalian cell lines, although nicked reduced diphtheria toxin inhibits cell-free protein synthesis of T. brucei and myeloma cells to the same extent as that of a rabbit reticulocyte lysate. The effect of diphtheria toxin on T. brucei in vitro translation is NAD+ dependent, suggesting that ADP-ribosylation of elongation factor 2 could be the cause of the inhibition as it is in mammalian cells. Thus, the toxic moiety of diphtheria toxin is suitable for preparation of cell-type-specific cytotoxic reagents directed towards trypanosomes.

journal_name

Mol Biochem Parasitol

authors

Scory S,Steverding D

doi

10.1016/s0166-6851(97)00162-x

subject

Has Abstract

pub_date

1997-12-01 00:00:00

pages

289-95

issue

1

eissn

0166-6851

issn

1872-9428

pii

S0166-6851(97)00162-X

journal_volume

90

pub_type

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