III. The Quest for Achille's Heel of Leishmania. Singular Targets as New Avenues for Drug DevelopmentChapter 12. Addressing the Molecular Biology of Leishmania for Drug Development

Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania. More than 20 Leishmania species infect humans and the disease is endemic in several areas of the Old and New World. Existing therapies for leishmaniasis are inadequate due to resistance, safety and cost, underscoring the necessity for safer therapies with alternative modes of action. The entry of molecular biology with its elucidation of the genomics and proteomics of these organisms has provided increasingly sophisticated explanations of their unique mechanisms to adapt to intense environmental pressures. An interesting feature of the Leishmania (and other trypanosomatids) genome is the unusual nature of transcription and RNA processing. Protein-coding genes are organized into long gene clusters, and the resulting polycistronic RNAs are post-transcriptionally processed into mature mRNAs by concomitant trans-splicing and polyadenylation. These and other unique features are not shared with its host, thus offering new and exciting new avenues for therapeutic intervention.