Genome-Wide Screening for Pathogenic Proteins and microRNAs Associated with Parasite–Host Interactions in Trypanosoma brucei

SIMPLE SUMMARY: Tsetse flies are blood-sucking insect vectors belonging to the order Diptera and are widely distributed in the areas of sub-Saharan Africa. These vectors can transmit the pathogenic parasite Trypanosoma brucei (T. brucei) which can cause a disease called African trypanosomiasis. Currently, discovering effective therapeutic drugs and vaccines with minor side effects is still one of the ongoing efforts to treat the disease as well as to prevent the epidemic. Genome technology has recently played an important role in uncovering the molecular mechanisms of many vector-borne diseases, which facilitates the identification of potential drug targets. To better understand the pathological contribution of parasite–host interactions to the disease, we studied the genomic and transcriptomic profiles of T. brucei. We identified a panel of pathogenic proteins and microRNAs supported by their molecular functions in T. brucei for the first time. Our study may pave a new avenue for designing preventive and therapeutic strategies to control this insect vector. ABSTRACT: Tsetse flies are a type of blood-sucking insect living in diverse locations in sub-Saharan Africa. These insects can transmit the unicellular parasite Trypanosoma brucei (T. brucei) which causes African trypanosomiasis in mammals. There remain huge unmet needs for prevention, early detection, and effective treatments for this disease. Currently, few studies have investigated the molecular mechanisms of parasite–host interactions underlying African trypanosomiasis, mainly due to a lack of understanding of the T. brucei genome. In this study, we dissected the genomic and transcriptomic profiles of T. brucei by annotating the genome and analyzing the gene expression. We found about 5% of T. brucei proteins in the human proteome, while more than 80% of T. brucei protein in other trypanosomes. Sequence alignment analysis showed that 142 protein homologs were shared among T. brucei and mammalian genomes. We identified several novel proteins with pathogenic potential supported by their molecular functions in T. brucei, including 24 RNA-binding proteins and six variant surface glycoproteins. In addition, 26 novel microRNAs were characterized, among which five miRNAs were not found in the mammalian genomes. Topology analysis of the miRNA-gene network revealed three genes (RPS27A, UBA52 and GAPDH) involved in the regulation of critical pathways related to the development of African trypanosomiasis. In conclusion, our work opens a new door to understanding the parasite–host interaction mechanisms by resolving the genome and transcriptome of T. brucei.