MicroMISTRANS · Error-prone protein synthesis in fungal pathogens Microsporidia: its scope and potential therapeutic targeting

Error-prone protein synthesis in fungal pathogens Microsporidia: its scope and potential therapeutic targeting

In this study, we explored animal parasites Microsporidia to understand one of the most fundamental problems in evolutionary biology – how parasitic lifestyles affect the activity and evolution of the molecular building blocks of a parasite cell. We believe this knowledge will help us create a new and revolutionary approach to eradicate currently incurable and deadly parasitic infections. Specifically, because most branches of microbial parasites are very different from each other at the molecular level, we frequently need to develop distinct therapies against distinct groups of parasites. However, emerging evidence shows that nearly all parasites share many similarities in the way they evolve, suggesting a potential basis for broad-range therapies against microbial parasites. In this study, we aimed to explore these common evolutionary tendencies in parasitic cells, studying protein synthesis machinery (also known as the ribosome) from microsporidian pathogen Encephalitozoon cuniculi. Using cryo-electron microscopy analysis, we described the molecular anatomy of microsporidian ribosomes, thereby answering the long-standing question in parasite biology: how do parasites retain the function of their molecular machines in the face of the extreme reduction of their molecular building blocks? In fact, for nearly two decades, microbial parasites were known for their extreme reduction of their molecular building blocks. Particularly, proteins and RNA molecules in microbial parasites are reduced to up to 50% of their size in free-living microorganisms. The objects of our study—microsporidian ribosomes—were predicted to lack multiple ribosomal proteins and up to a third of rRNA nucleotides compared to free-living species. How these molecules are nonetheless functional in parasites remained largely a riddle. Our study showed that parasites use many molecular tricks to retain the biological activity of their ribosomes, providing a better understanding of how parasites cope with a drastic reduction of their molecular building blocks. Collectively, our work helped to better understand the fundamental difference between parasites and their hosts (in terms of how each of these two groups of organisms is designed at the molecular level), providing new knowledge for combating microbial pathogens.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз