MALARIA PARASITES REGULATE SECRETION OF EXOSOMES CARRYING GENOMIC DNA

Neta Regev-Rudzki 1,2 Xavier Sisquella 2 Matthew Pimentel 2 Jocelyn Sietsma Penington 2 Jennifer C. Volz 2 Anthony T. Papenfuss 2
1Biological Chemistry, Weizmann Institute of Science, Rehovot
2Department of Medical Biology, The Walter and Eliza Hall Institute of Medical Research, The University of Melbourne, Melbourne

Cells use extracellular vesicles to communicate, to coordinate social activities and, in the case of pathogens, to export virulence effectors into host target cells. Previously, we showed that the lethal malaria parasites directly communicate within a population using exosome-like vesicles that are capable of delivering episomal plasmids and these are produced at the ring-stage of the asexual life cycle. Here, we identify these nanovesicles as exosomes and determine their molecular content; nucleic acids, proteins and lipids. By establishing advanced nano-resolution techniques for analysing exosome content, we discovered that the exosomes deliver endogenous nuclear genes, parasite apicoplast and mitochondrial genomic DNA. Interestingly, these genes are partially transferred into mosquito tissue by feeding, raising the possibility of potential cargo delivery to modulate vector cells. Moreover, we show that the nucleotide cargo is packaged into released exosomes only at the early stage of parasite development in host (infected red blood cells), highlighting the selectivity of this process. Our work identifies previously unknown molecular players in signalling pathway of malaria parasite and provides a new insight into our understanding of how malaria parasites can manipulate their host environment.









Powered by Eventact EMS