Gene expression profile comparison of peptidases and their inhibitors in Schistosoma mansoni and Fasciola hepatica eggs
Abstract
The eggs of the blood fluke Schistosoma mansoni (SM) are the main cause of the pathological manifestations of the serious neglected tropical disease schistosomiasis. Adult worms reproduce in the mesenteric veins and lay eggs into the bloodstream.
The eggs either migrate from the blood vessel across the intestinal wall into the gut lumen or are carried away and become tissue-entrapped, typically in the liver. During these processes, eggs secrete molecules that interact with the host.
They influence the surrounding host blood and tissue environment and modulate an immune response. This study aimed to identify what egg peptidases and peptidase inhibitors may be involved during the infection.
Additionally, a comparison with eggs of another trematode Fasciola hepatica (FH) was included. FH eggs pass from host bile ducts to the gut lumen and outer environment without any known pathological consequences for the host and without penetrating the tissues.
Therefore, this organism is a suitable comparative subject to decipher which peptidases and inhibitors are common and which are exclusive for each of the species. Eggs were collected, divided into two groups of mature and immature eggs, and their RNA was extracted.
Using Illumina RNA sequencing and bioinformatic analysis, a comprehensive dataset showing transcription levels of all SM and FH genes was generated. By a combination of automatic database searches and manual curation, peptidases and peptidase inhibitors expressed by eggs were identified and annotated.
This work reveals that SM eggs transcribe over 130 peptidases and 21 peptidase inhibitors. Most of the expressed SM peptidases are orthologous to FH peptidases (65%).
In contrast, only two SM peptidase inhibitors have orthologous counterparts expressed by FH eggs. As a result of differential expression analysis, it was observed that transcription of 13 and 15 peptidases is upregulated in mature and immature eggs, respectively.
Surprisingly, among peptidase inhibitors, alpha-2-macroglobulin was found to be the second most transcribed, mainly in immature eggs. This study is the first to generate and describe a broad spectrum of peptidases and their inhibitors transcribed by SM eggs.
Based on the findings of this study, we pinpoint a group of previously unstudied molecules that are most likely important for the egg-host interaction.