Characterisation of cloned lines of Trypanosoma brucei expressing stable resistance to MelCy and suramin.
Two cloned drug-sensitive stocks of Trypanosoma brucei (STIB 247 and STIB 386) were each used to generate cloned lines expressing resistance to the melaminophenyl arsenical drug cymelarsan (247MelCyR and 386MelCyR) and to suramin (247SurR and 386SurR). The drug-resistance phenotypes were stable after passaging in mice in the absence of drug pressure and three of the lines were transmitted through tsetse flies with no alteration of drug-resistance. There was no evidence of cross-resistance between melCy and suramin in vivo. Twenty-four hour growth inhibition assays were conducted on bloodstream and procyclic forms in axenic in vitro cultures. Suramin-resistance was expressed in bloodstream forms but not in the procyclic stage, while the melCy-resistant lines expressed melCy-resistance in both stages. No cross-resistance between melCy and suramin was observed. Cross-resistance between melCy and another arsenical drug, melB (melarsoprol), was observed in vivo, but to only a very limited extent in vitro. We propose that this difference between the in vivo and in vitro results for melB may indicate that an alteration in a surface adenosine transporter responsible for reduced melCy uptake was bypassed by melB over 24 hours in vitro.
Scott
A G
AG
Parasitology Laboratory, University of Glasgow, UK. ags@bioch.ox.ac.uk
Tait
A
A
Turner
C M
CM
D000818:Animals; D001152:Arsenicals / Q000494:pharmacology*; D001681:Biological Assay; D002478:Cells, Cultured; D002999:Clone Cells; D004351:Drug Resistance; D005260:Female; D008297:Male; D008549:Melarsoprol / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D013498:Suramin / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000235:genetics
D001152:Arsenicals; D014344:Trypanocidal Agents; D013498:Suramin; C062789:melaminylthioarsenate; D008549:Melarsoprol