African trypanosomes expressing multiple VSGs are rapidly eliminated by the host immune system
Significance Many parasites escape the host immune system by undergoing antigenic variation, a process in which surface antigens are regularly shed and replaced by new ones. Trypanosoma brucei employs multiple sophisticated molecular mechanisms to ensure the expression of a homogeneous VSG coat. We generated a mutant parasite that expresses multiple distinct VSGs and studied the consequences of having a multi-VSG coat during an infection. We showed that expression of multiple VSGs makes the parasites more vulnerable to the immune response, which can now control the trypanosomes from the onset of the infection, allowing most mice to survive. In the future, trypanosome infections may be treat…
A long non-coding RNA controls parasite differentiation in African trypanosomes
Trypanosoma bruceicauses African sleeping sickness, a fatal human disease. Its differentiation from replicative slender form into quiescent stumpy form promotes host survival and parasite transmission. Long noncoding RNAs (lncRNAs) are known to regulate cell differentiation. To determine whether lncRNAs are involved in parasite differentiation we used RNAseq to survey theT. bruceilncRNA gene repertoire, identifying 1,428 previously uncharacterized lncRNA genes. We analysedgrumpy, a lncRNA located immediately upstream of an RNA-binding protein that is akeydifferentiation regulator. Grumpy over-expression resulted in premature parasite differentiation into the quiescent stumpy form, and subse…