Detection of arsenical drug resistance in Trypanosoma brucei with a simple fluorescence test.
The resurgence of human African trypanosomiasis (HAT), coupled with an increased incidence of drug resistance, is of concern. We report a quick, simple, and sensitive test for identification of parasites resistant to melarsoprol, the main drug used to treat late stage HAT. Resistant parasites are defective in a plasma membrane transporter responsible for drug uptake. The same transporter carries the fluorescent diamidine DB99 (2,5-bis-(4-amidinophenyl)-3,4-dimethylfuran) into trypanosomes. The two DNA-containing structures in the trypanosome--the nucleus and the kinetoplast--begin to fluoresce within 1 min of introduction of DB99, unless drug resistant.
Stewart
Mhairi L
ML
University of Glasgow, Division of Infection and Immunity, Institute of Biomedical and Life Sciences, The Joseph Black Building, Glasgow G12 8QQ, UK.
Krishna
Sanjeev
S
Burchmore
Richard J S
RJ
Brun
Reto
R
de Koning
Harry P
HP
Boykin
David W
DW
Tidwell
Richard R
RR
Hall
J Ed
JE
Barrett
Michael P
MP
D000818:Animals; D001152:Arsenicals / Q000494:pharmacology; D003958:Diamide; D004351:Drug Resistance; D005453:Fluorescence; D008549:Melarsoprol / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests / Q000379:methods; D033703:Nucleoside Transport Proteins / Q000378:metabolism; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000378:metabolism
D001152:Arsenicals; D033703:Nucleoside Transport Proteins; C486446:P2 transporter, Trypanosoma brucei; D014344:Trypanocidal Agents; D003958:Diamide; C062789:melaminylthioarsenate; D008549:Melarsoprol