Cell differentiation and infectivity of Leishmania mexicana are inhibited in a strain resistant to an ABC-transporter blocker.
We analysed whether markers of cell differentiation and infectivity differed when compared to the parental sensitive strain [NR(Gs)] in an in vitro selected Leishmania strain [NR(Gr)] resistant to Glibenclamide, an ATP-binding-cassette (ABC)-transporter blocker. The data show that the cell body area was larger in NR(Gr) compared to NR(Gs) and that functional characters associated with an infective metacyclic phenotype, such as resistance to the lytic effect of the alternative complement pathway and expression of the Meta-1 protein, were reduced. The infectivity of NR(Gr) to J774.1 macrophages was also significantly reduced. These results suggest that resistance in Leishmania against Glibenclamide, a general blocker of P-glycoproteins, could produce functional modifications that may be relevant for Leishmania differentiation, infectivity and survival.
Silva
N
N
Laboratory of Molecular Physiology, Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela.
Camacho
N
N
Figarella
K
K
Ponte-Sucre
A
A
D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology*; D004351:Drug Resistance; D005905:Glyburide / Q000494:pharmacology*; D006801:Humans; D007894:Leishmania mexicana / Q000166:cytology / Q000187:drug effects* / Q000472:pathogenicity*; D016773:Leishmaniasis, Cutaneous / Q000469:parasitology*; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D015800:Protozoan Proteins; D005905:Glyburide