Sequential Membrane Rupture and Vesiculation during Plasmodium berghei Gametocyte Egress from the Red Blood Cell

Andreadaki, Maria; Hanssen, Eric; Deligianni, Elena; Claudet, Cyrille; Wengelnik, Kai; Mollard, Vanessa; McFadden, Geoffrey I.; Abkarian, Manouk; Braun-Breton, Catherine; Sidén‐Kiamos, Inga

doi:10.1038/s41598-018-21801-3

Cited by 29 publications

(39 citation statements)

References 43 publications

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“…Whereas a female gametocyte only forms one spherical macrogamete, a male gametocyte undergoes three rounds of DNA replication to produce eight flagella‐like gametes, each consisting of an axoneme and a nucleus encased by a flagellar membrane (Kuehn & Pradel, 2010). Egress from the erythrocyte membrane is an important step of gametogenesis and requires multiple factors for the sequential lysis of PVM and the erythrocyte membrane (Andreadaki et al, 2018; Deligianni et al, 2013; Sologub et al, 2011; Wirth & Pradel, 2012). Several factors affect the egress of both male and female gametocytes.…”

Section: Discussionmentioning

confidence: 99%

“…The egress of fully differentiated gametes from the erythrocyte requires the lysis of two membranes surrounding the parasite: the inner parasitophorous vacuole membrane (PVM) and the outer erythrocyte membrane (Deligianni et al, 2013; Sologub et al, 2011). The activated gametocytes emerging from the erythrocyte follow a sequential, inside‐out mode, in which rupture of PVM occurs during the first minutes after gametocyte activation, while the rupture of erythrocyte membrane occurs several minutes later (Andreadaki et al, 2018). Subsequently, the micro‐ and macro‐gametes fuse to form a diploid zygote, which transforms into a motile ookinete that penetrates the midgut epithelium to form an oocyst (Bousema & Drakeley, 2011; Paul, Brey, & Robert, 2002).…”

Section: Introductionmentioning

confidence: 99%

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A conserved malaria parasite antigen Pb22 plays a critical role in male gametogenesis inPlasmodium berghei

Liu

Yang

Wang

et al. 2020

Cellular Microbiology

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Gametogenesis, the formation of gametes from gametocytes, an essential step for malaria parasite transmission, is targeted by transmission‐blocking drugs and vaccines. We identified a conserved protein (PBANKA_0305900) in Plasmodium berghei, which encodes a protein of 22 kDa (thus named Pb22) and is expressed in both asexual stages and gametocytes. Its homologues are present in all Plasmodium species and its closely related, Hepatocystis, but not in other apicomplexans. Pb22 protein was localised in the cytosols of schizonts, as well as male and female gametocytes. During gamete‐to‐ookinete development, Pb22 became localised on the plasma membranes of gametes and ookinetes. Compared to the wild‐type (WT) parasites, P. berghei with pb22 knockout (KO) showed a significant reduction in exflagellation (~89%) of male gametocytes and ookinete number (~97%) during in vitro ookinete culture. Mosquito feeding assays showed that ookinete and oocyst formation of the pb22‐KO line in mosquito midguts was almost completely abolished. These defects were rescued in parasites where pb22 was restored. Cross‐fertilisation experiments with parasite lines defective in either male or female gametes confirmed that the defects in the pb22‐KO line were restricted to the male gametes, whereas female gametes in the pb22‐KO line were fertile at the WT level. Detailed analysis of male gametogenesis showed that 30% of the male gametocytes in the pb22‐KO line failed to assemble the axonemes, whereas ~48.9% of the male gametocytes formed flagella but failed to egress from the host erythrocyte. To explore its transmission‐blocking potential, recombinant Pb22 (rPb22) was expressed and used to immunise mice. in vitro assays showed that the rPb22‐antisera significantly inhibited exflagellation by ~64.8% and ookinete formation by ~93.4%. Mosquitoes after feeding on rPb22‐immunised mice also showed significant decreases in infection prevalence (83.3–93.3%) and oocyst density (93.5–99.6%). Further studies of the Pb22 orthologues in human malaria parasites are warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A conserved malaria parasite antigen Pb22 plays a critical role in male gametogenesis inPlasmodium berghei

Liu

Yang

Wang

et al. 2020

Cellular Microbiology

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“…Upon discharge, PPLP2 perforates the RBCM, resulting in the release of the RBC cytoplasm [ 70 , 71 ]. Noteworthy, the male and female gametes that have meanwhile formed are still contained in the remnants of the RBCM for several more minutes, before the RBCM opens via a single pore to release the fertile gametes [ 71 - 73 ]. The delayed cell exit might represent a way to circumvent the host's immune system.…”

Section: Exit Pathwaysmentioning

confidence: 99%

Pathways of host cell exit by intracellular pathogens

Flieger¹,

Frischknecht

Häcker³

et al. 2018

Microb Cell

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Host cell exit is a critical step in the life-cycle of intracellular pathogens, intimately linked to barrier penetration, tissue dissemination, inflammation, and pathogen transmission. Like cell invasion and intracellular survival, host cell exit represents a well-regulated program that has evolved during host-pathogen co-evolution and that relies on the dynamic and intricate interplay between multiple host and microbial factors. Three distinct pathways of host cell exit have been identified that are employed by three different taxa of intracellular pathogens, bacteria, fungi and protozoa, namely (i) the initiation of programmed cell death, (ii) the active breaching of host cellderived membranes, and (iii) the induced membrane-dependent exit without host cell lysis. Strikingly, an increasing number of studies show that the majority of intracellular pathogens utilize more than one of these strategies, dependent on life-cycle stage, environmental factors and/or host cell type. This review summarizes the diverse exit strategies of intracellular-living bacterial, fungal and protozoan pathogens and discusses the convergently evolved commonalities as well as system-specific variations thereof. Key microbial molecules involved in host cell exit are highlighted and discussed as potential targets for future interventional approaches.

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“…For mating to occur, gametes must egress from the host RBC. This process takes place by successive inside-out rupture of two membranes surrounding blood stage parasites, the parasitophorous vacuole membrane (PVM) and RBC plasma membrane (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Gender-related Secretome of Plasmodium berghei Sexual Stages

Grasso

Mochi

Fratini

et al. 2020

Molecular & Cellular Proteomics

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Plasmodium, the malaria parasite, undergoes a complex life cycle alternating between a vertebrate host and a mosquito vector of the genus Anopheles. In red blood cells of the vertebrate host, Plasmodium multiplies asexually or differentiates into gamete precursors, the male and female gametocytes, responsible for parasite transmission. Sexual stage maturation occurs in the midgut of the mosquito vector, where male and female gametes egress from the host erythrocytes to fuse and form a zygote. Gamete egress entails the successive rupture of two membranes surrounding the parasite, the parasitophorous vacuole membrane and the erythrocyte plasma membrane. In this study, we used the rodent model parasite Plasmodium berghei to design a label-free quantitative proteomic approach aimed at identifying gender-related proteins differentially released/secreted by purified mature gametocytes when activated to form gametes. We compared the abundance of molecules secreted by wild type gametocytes of both genders with that of a transgenic line defective in male gamete maturation and egress. This enabled us to provide a comprehensive dataset of egress-related molecules and their gender specificity. Using specific antibodies, we validated eleven candidate molecules, predicted as either gender-specific or common to both male and female gametocytes. All of them localize to punctuate, vesicle-like structures that relocate to cell periphery upon activation, but only three of them localize to the gametocyte-specific secretory vesicles named osmiophilic bodies. Our results confirm that the egress process involves a tightly coordinated secretory apparatus that includes different types of vesicles and may put the basis for functional studies aimed at designing novel transmission-blocking molecules.

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Sequential Membrane Rupture and Vesiculation during Plasmodium berghei Gametocyte Egress from the Red Blood Cell

Cited by 29 publications

References 43 publications

A conserved malaria parasite antigen Pb22 plays a critical role in male gametogenesis inPlasmodium berghei

A conserved malaria parasite antigen Pb22 plays a critical role in male gametogenesis inPlasmodium berghei

Pathways of host cell exit by intracellular pathogens

A Comprehensive Gender-related Secretome of Plasmodium berghei Sexual Stages

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