The Eukaryotic Elongation Factor 1 Alpha (eEF1α) from the Parasite Leishmania infantum Is Modified with the Immunomodulatory Substituent Phosphorylcholine (PC)

Abstract

Proteins and glycolipids have been found to be decorated with phosphorylcholine (PC) both in protozoa and nematodes that parasitize humans and animals. PC epitopes can provoke various effects on immune cells leading to an immunomodulation of the host’s immune system that allows long-term persistence of the parasites. So far, only a limited number of PC-modified proteins, mainly from nematodes, have been identified. Infections caused by Leishmania spp. (e.g., L. infantum in southern Europe) affect about 12 million people worldwide and are characterized by a wide spectrum of clinical forms in humans, ranging from cutaneous to fatal visceral leishmaniasis. To establish and maintain the infection, these protozoa are dependent on the secretion of effector molecules into the host for modulating their immune system. In this project, we analyzed the PC modification of L. infantum promastigotes by 2D-gel based proteomics. Western blot analysis with the PC-specific antibody TEPC-15 revealed one PC-substituted protein in this organism, identified as eEF1α. We could demonstrate that the binding of eEF1α to one of its downstream effectors is dependent on its PC-modification. In this study we provide evidence that in this parasite the modification of eEF1α with PC may be essential for its function as an important virulence factor.

Revisiting the heterogeneous global genomic population structure of Leishmania infantum

“…3c). These findings highlighted and confirmed the importance of these genes in L. infantum as possible mechanisms of survival and adaptation in both the vector and the mammal host [69]. Finally, we identified an increase in genes involved in the transport and homeostasis of zinc (a component crucial in the cellular functions of this parasite) [70].…”

Parasitomimetics: Can We Utilize Parasite-Derived Immunomodulatory Molecules for Interventions to Immunological Disorders?

“…GP63 also cleaves mTOR and dephosphorylates 4E-BP1, resulting in transcriptional repression and macrophage suppression ( 37 ). SHP-1-mediated suppression of macrophages is dependent not only on cleavage by GP63, and another leishmanial protein elongation factor-1alpha (EF-1α) binds to and activates SHP-1, which in turn inhibits macrophage activation ( 40 , 41 ). This ability of Leishmania to inhibit macrophage effector functions may result from direct interference by Leishmania molecules such as GP63 and EF-1α with macrophage signal transduction pathways.…”

Revisiting the Schistosoma japonicum life cycle transcriptome for new insights into lung schistosomula development

“…Conserved in many organisms, eEf1α plays a central role in eukaryotic protein synthesis (Billaut-Mulot, et al, 1994). Functionally, eEF1α is an enzyme responsible for the catalysis of the GTP-dependent binding of aminoacylated-tRNAs to the A site of the ribosome (Timm, et al, 2017, Wang, et al, 2017. However, eEf1α also plays a key role in functions other than translation, including apoptosis (Alves, et al, 2015).…”

“…The membranes of the schistosome tegument are enriched in abundant phospholipid classes such as phosphatidylcholine (PC) (Retra, et al, 2015), which has also been identified in the S. mansoni lipidome (Giera, et al, 2018). Leishmania infantum are able to form PC-epitopes through the active modification of the eEF1 protein (Timm, et al, 2017). L.…”