SUMO chains depolymerization induces slender to stumpy differentiation in T. brucei bloodstream parasites

Abstract

Trypanosoma brucei are extracellular protozoan parasites transmitted by tsetse flies that cause sleeping sickness in humans and nagana in cattle. Inside the mammalian host, differentiation from a bloodstream replicative slender form into a quiescent stumpy form allows the persistence of the parasite and the spread of the infection. SUMOylation is a reversible and dynamic post-translational modification of proteins that regulates diverse nuclear processes, such as DNA replication, repair and transcription. SUMO can be attached to its target proteins either as a single monomer or forming polymeric chains. We found that transgenic cell lines able to conjugate SUMO just as a monomer are attenuated in vivo. SUMO chain mutant monomorphic parasites display relapsing and remitting waves of parasitemia, at variance with wild-type parasites that cause unremitting parasitemia and mice death. Furthermore, when mice are infected with an analogous SUMO chain mutant generated in a differentiation-competent pleomorphic background, stumpy cells can be observed at unusually low parasitemia values. Our study reveals that SUMO depolymerization could represent a coordinated signal triggered during a quiescence activation program.