Overexpression of Leishmania major protein arginine methyltransferase 6 reduces parasite infectivity in vivo

Arginine methylation is catalysed by Protein Arginine Methyltransferases (PRMTs) and can affect how a target protein functions and how it interacts with other macromolecules, which in turn impacts on cell metabolism and gene expression control. Leishmania parasites express five different PRMTs, and although the presence of each individual PRMT is not essential per se, the imbalanced activity of these PRMTs can impact the virulence of Leishmania parasites in vitro and in vivo. Here we created a Leishmania major cell line overexpressing PRMT6 and show that similar to what was observed for the T. brucei homologous enzyme, L. major PRMT6 probably has a narrow substrate range. However, its overexpression notably impairs the infection in mice, with a mild reduction in the number of viable parasites in the lymph nodes. Our results indicate that arginine methylation by LmjPRMT6 plays a significant role in the adaptation of the parasite to the environment found in the mammalian host.

Automated summary

Arginine methylation by PRMTs affects protein function, protein-protein interactions, cell metabolism, and gene expression control. Leishmania parasites express five PRMTs, and their imbalanced activity can impact parasite virulence. Overexpression of PRMT6 in Leishmania major impairs infection in mice, resulting in reduced parasite numbers in lymph nodes. Our findings suggest a significant role of LmjPRMT6-mediated arginine methylation in parasite adaptation to the mammalian host environment.