Abstract
ABSTRACTThe intracellular lifestyle represents a challenge for the rapidly proliferating liver stage Plasmodium parasite. In order to scavenge host resources, Plasmodium has evolved the ability to target and manipulate host cell organelles. Using dynamic fluorescence-based imaging, we here show an interplay between the pre-erythrocytic stages of Plasmodium berghei and the host cell Golgi during liver stage development. Liver stage schizonts fragment the host cell Golgi into miniaturized stacks, which increases surface interactions with the parasitophorous vacuolar membrane of the parasite. Expression of specific dominant-negative Arf1 and Rab GTPases, which interfere with the host cell Golgi-linked vesicular machinery, results in developmental delay and diminished survival of liver stage parasites. Moreover, functional Rab11a is critical for the ability of the parasites to induce Golgi fragmentation. Altogether, we demonstrate that the structural integrity of the host cell Golgi and Golgi-associated vesicular traffic is important for optimal pre-erythrocytic development of P. berghei. The parasite hijacks the Golgi structure of the hepatocyte to optimize its own intracellular development.This article has an associated First Person interview with the first author of the paper.
Highlights
Malaria is a mosquito-borne infectious disease caused by parasites of the genus Plasmodium
Recruitment of the host cell Golgi to the P. berghei parasitophorous vacuolar membrane (PVM) Using quantitative fluorescence microscopy, we characterized the relationship of P. berghei parasites to the hcGolgi during the preerythrocytic development
Imaging of the trans-Golgi network (TGN) was performed on HeLa cells transiently expressing the trans-Golgi enzyme GalT–GFP (Fig. 1A) as well as Huh-7 cells stained for the endogenous Golgin97, a peripheral membrane protein on the cytoplasmic face of the TGN (Fig. 1B)
Summary
Malaria is a mosquito-borne infectious disease caused by parasites of the genus Plasmodium. The parasitophorous vacuolar membrane (PVM) is the interface between the host cell cytosol, and the developing parasite. The role of the PVM and its molecular composition in liver stages is not fully understood, this structure is thought to play a key role in nutrient acquisition (Bano et al, 2007; Fougere et al, 2016; Grützke et al, 2014; Petersen et al, 2017), waste disposal and protection of the parasite from the host cell intracellular defense system (Agop-Nersesian et al, 2017; Boonhok et al, 2016; Grüring et al, 2012; Prado et al, 2015; Real et al, 2018; Spielmann et al, 2012). Key elements include the generation of an export machinery, modification of PVM permeability to enable the uptake of cytosolic metabolites, and subversion of host cell organelles (Agop-Nersesian et al, 2018; Ingmundson et al, 2014; Spielmann et al, 2012)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call