Lab study maps 170 tRNA modification sites in Chagas parasite

Under bright-field microscopy, Trypanosoma cruzi is more than a fixed shape: the parasite that causes Chagas disease changes its proteins as it moves through its life cycle. A team led by Satoshi Kimura of Cornell University and Julia Pinheiro Chagas da Cunha of Brazil’s Butantan Institute has now mapped part of the molecular switch that helps it become infectious.

The researchers identified 170 sites of chemical modification on transfer RNA, or tRNA. These molecules deliver amino acids to the machinery that builds proteins. The sites varied between the parasite’s infectious and noninfectious forms, suggesting that tRNA changes help control the shift between them.

To make the map, the team combined tRNA sequencing, mass spectrometry and bioinformatics. They then used CRISPR gene editing—a tool for altering genes—to examine what happened when one of the modifications was missing during the parasite’s transition. Recent improvements in tRNA-sequencing methods made the work possible; the molecules’ modifications had previously made them difficult to read efficiently.

The biology matters because the infectious form, called a metacyclic trypomastigote, is excreted by infected kissing bugs and invades mammals. The parasite’s epimastigote form, by contrast, is noninfective and replicates inside the insect. Chagas disease affects approximately 7 million people worldwide, and its two approved drugs, benznidazole and nifurtimox, work best when infection is found early.

So what changes in practice? Not treatment today. The study gives researchers a set of mechanisms that could eventually be explored as drug targets, while its authors say considerable research remains. The finding is a laboratory step toward understanding a parasite that can remain in the body for decades and cause heart or digestive problems in its chronic phase.