Efflux systems and increased trypanothione levels in arsenite-resistant Leishmania.
The mechanism of resistance to the metal arsenite has been studied and compared in L. mexicana, L. tropica, and L. tarentolae selected in a step by step manner for arsenite resistance. Amplification of the ABC transporter gene pgpA was found to be a frequent resistance mechanism in all species. Transfection of pgpA genes into different species indicated that both the origin of the pgpA gene and the recipient strain into which the gene is transfected seem important for resistance. An increase in the levels of trypanothione was also correlated with metal resistance in different Leishmania species. The mechanism used to increase the levels of trypanothione seems to differ, however, between the different species. This study points to a key role of transporters and thiol levels in metal resistance in Leishmania.
Légaré
D
D
Centre de Recherche en Infectiologie du Centre de Recherche du CHUL, Faculté de Médecine, Université Laval, Québec, Canada.
Papadopoulou
B
B
Roy
G
G
Mukhopadhyay
R
R
Haimeur
A
A
Dey
S
S
Grondin
K
K
Brochu
C
C
Rosen
B P
BP
Ouellette
M
M
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D018053:Arsenites / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport; D004351:Drug Resistance; D005784:Gene Amplification; D005978:Glutathione / Q000031:analogs & derivatives*; D007891:Leishmania / Q000187:drug effects* / Q000235:genetics; D007894:Leishmania mexicana / Q000187:drug effects / Q000235:genetics; D007895:Leishmania tropica / Q000187:drug effects / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008954:Models, Biological; D009154:Mutation; D015800:Protozoan Proteins; D013045:Species Specificity; D013095:Spermidine / Q000031:analogs & derivatives*; D013438:Sulfhydryl Compounds / Q000032:analysis
D018528:ATP-Binding Cassette Transporters; D018053:Arsenites; D008562:Membrane Glycoproteins; C106891:PgpA protein, Leishmania; D015800:Protozoan Proteins; D013438:Sulfhydryl Compounds; C044809:trypanothione; D005978:Glutathione; D013095:Spermidine