AQP1 gene overexpression was found

AQP1 gene overexpression was found in 3 resistant isolates, a paradoxical observation considering that AQP1 plays a role in drug entry. In fact, AQP1 is a membranous channel through which the trivalent antimony enters the parasite, and AQP1 overexpression is typically observed in susceptible isolates (11, 45, 47). However, a few cases of AQP1 overexpression in L. donovani-resistant clinical isolates have been reported (18, 19). As the regulation of gene expression in Leishmania occurs primarily at the posttranscriptional level, the overexpression of AQP1 may be modulated at the protein level. Moreover, we cannot exclude the possibility of a mutation of the AQP1 gene that produces a nonfunctional protein in the resistant isolates displaying AQP1 overexpression.