Functional cloning as a means to identify Leishmania genes involved in drug resistance

Resistance to anti-leishmanial drugs is a mounting problem in high-endemicity regions of South Asia and, potentially, in the context of HIV-Leishmania coinfections in Southern Europe. The molecular basis for clinical drug resistance is still largely unknown. It is important, however, to identify all relevant drug resistance markers for further drug development and for epidemiological surveys. An elegant and powerful method to identify such drug resistance markers without bias is functional cloning, using cosmid-based genomic DNA libraries. This review discusses the merits and caveats of this approach.