Evolution of catalase in Trypanosomatidae

Abstract text

Catalase is one of the most abundant enzymes on Earth. It decomposes hydrogen peroxide, thus protecting cells from dangerous reactive oxygen species. The catalase-encoding gene is conspicuously absent from the genome of most representatives of the family Trypanosomatidae. The exceptions are monoxenous relatives of Leishmania spp., and representatives of the genera Blastocrithidia, Obscuromonas, and Vickermania. In this work, we expressed the Leptomonas seymouri-derived catalase from the Leishmania mexicana beta-tubulin locus using a novel bicistronic expression system, which relies on the 2A peptide of Teschovirus A. We demonstrated that catalase-expressing parasites are severely compromised in their ability to develop in insects, to be transmitted and to infect mice, and to cause clinical manifestation in their mammalian host. Taken together, our data support the hypothesis that the presence of catalase is not compatible with the dixenous life cycle of Leishmania, resulting in loss of this gene from the genome during the evolution of these parasites. In addition, we ablated a catalase-encoding gene from the Leptomonas seymouri genome and demonstrated that parasites' development in vivo depends on the expression level of this enzyme. These studies were compelmented by biochemical characterization of three independently-acquired catalases (of Blastocrithidia, Leptomonas, and Vickermania) in vitro.