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Article
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Differentiation granules, a dynamic regulator of T. brucei development
The African trypanosome Trypanosoma brucei has been shown to form stress granules in vitro that might be repurposed to enable differentiation and facilitate parasite transmission. Here, Cayla et al. show that differentiation between slender and stumpy forms does involve membrane-less granules that are different from nutritional stress granules.
- Mathieu Cayla
- , Christos Spanos
- & Keith R. Matthews
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Article
| Open Access
Atypical flagella assembly and haploid genome coiling during male gamete formation in Plasmodium
Gametogenesis is critical for sexual reproduction. Using volume electron microscopy, Hair et al report the structural organisation of the haploid nucleus coiled around the axoneme of the Plasmodium berghei male microgamete.
- Molly Hair
- , Flávia Moreira-Leite
- & Sue Vaughan
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Article
| Open Access
Encystation stimuli sensing is mediated by adenylate cyclase AC2-dependent cAMP signaling in Giardia
Giardia lamblia is an established model for studying encystation. Shih et al show bile and alkaline pH induce changes in membrane ordering, upregulate cAMP, and initiate encystation gene expression.
- Han-Wei Shih
- , Germain C. M. Alas
- & Alexander R. Paredez
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| Open Access
A PPP-type pseudophosphatase is required for the maintenance of basal complex integrity in Plasmodium falciparum
The authors discover a pseudophosphatase that is an essential component of the basal complex, a contractile ring required for cell division of the malaria parasite. Using a combination of genetics, biochemistry, and cell biology techniques, they demonstrate that the pseudophosphatase, PfPPP8, is critical for integrity and contraction of the basal complex.
- Alexander A. Morano
- , Rachel M. Rudlaff
- & Jeffrey D. Dvorin
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EB1 decoration of microtubule lattice facilitates spindle-kinetochore lateral attachment in Plasmodium male gametogenesis
EB are conserved microtubule (MT) plus-end binding proteins. Here, Yang et al. report that Plasmodium EB1 possesses distinct MT-lattice affinity and decorates the full-length of spindle MTs. Gene deletion impairs the spindle-kinetochore lateral attachment, leading to anucleated male gametes.
- Shuzhen Yang
- , Mengya Cai
- & Jing Yuan
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Article
| Open Access
Apical anchorage and stabilization of subpellicular microtubules by apical polar ring ensures Plasmodium ookinete infection in mosquito
The structure of subpellicular microtubules (SPMTs) nucleated from the apical polar ring (APR) is essential for Plasmodium parasite morphogenesis, gliding motility, and invasion. Here, Qian et al. characterize the function of APR2 protein in P. yoelii ookinetes. Using co-localization analysis, proximity labeling, CoIP, expansion microscopy and FRAP, they show that APR2 binds to SMPTs and has a fixed position in APR. Deletion mutants fail to traverse the mosquito midgut as they fail to anchor SPMTs on APR, which affects invasive morphology and gliding motility.
- Pengge Qian
- , Xu Wang
- & Jing Yuan
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Heme-deficient metabolism and impaired cellular differentiation as an evolutionary trade-off for human infectivity in Trypanosoma brucei gambiense
Decreased functionality and expression of trypanosome haptoglobin-hemoglobin receptor (HpHbR) is one of the evolutionary modifications that have allowed Trypanosoma brucei gambiense to infect humans. Here, Horakova et al. show that hemoglobin uptake in African trypanosomes is mediated almost exclusively by HpHbR and relevant for slender-to-stumpy differentiation. T. b. gambiense is poorly competent to differentiate into stumpy forms compared to T. b. brucei, due to reduced functionality of HpHbR.
- Eva Horáková
- , Laurence Lecordier
- & Julius Lukeš
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Repurposing the mitotic machinery to drive cellular elongation and chromatin reorganisation in Plasmodium falciparum gametocytes
The sexual blood stages of Plasmodium falciparum develop through five morphologically distinct stages culminating in mature crescent-shaped gametocytes that can be transmitted from the mammalian host to the mosquito vector. Here, Li et al. apply different microscopy and tomography approaches to characterize how the microtubule organizing center and cytoplasmic and nuclear microtubules are organized and oriented during these different stages in the absence of genome replication and mitosis.
- Jiahong Li
- , Gerald J. Shami
- & Leann Tilley
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| Open Access
Monomeric prefusion structure of an extremophile gamete fusogen and stepwise formation of the postfusion trimeric state
Studies in the postfusion structures of the conserved gamete fusogen HAP2 show a trimeric state typical of viral class II fusion proteins. Here, the authors present the crystal structure of a prefusion state of Cyanidioschyzon merolae HAP2 and low resolution structures of intermediates in the pathway to its trimeric postfusion state.
- Juan Feng
- , Xianchi Dong
- & Timothy A. Springer
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Article
| Open Access
Extracellular release of two peptidases dominates generation of the trypanosome quorum-sensing signal
Trypanosomes use quorum-sensing (QS) signalled by oligopeptides to generate transmission-competent stumpy forms. Here, Tettey et al. perform mass spectrometry analysis to identify secreted peptidases and systematically assess each of the identified candidates for their role in stumpy formation in vivo. Two enzymes, oligopeptidase B and metallocarboxypeptidase 1 are shown to dominate QS.
- Mabel Deladem Tettey
- , Federico Rojas
- & Keith R. Matthews
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| Open Access
Defining the early stages of intestinal colonisation by whipworms
Whipworms are large parasites causing chronic disease in humans and other mammals. Here, the authors show how larvae create tunnels inside the gut lining and reveal the early host response to infection via Isg15 in mice and murine caecaloids.
- María A. Duque-Correa
- , David Goulding
- & Matthew Berriman
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Bicyclic azetidines target acute and chronic stages of Toxoplasma gondii by inhibiting parasite phenylalanyl t-RNA synthetase
Current treatments for toxoplasmosis are limited by adverse reactions and inability to cure chronic infections dominated by semi-dormant cyst forms. Here the authors demonstrate the potential of small molecule inhibitors of PheRS for controlling acute and chronic toxoplasmosis.
- Joshua B. Radke
- , Bruno Melillo
- & L. David Sibley
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Article
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CRISPR/Cas9-engineered inducible gametocyte producer lines as a valuable tool for Plasmodium falciparum malaria transmission research
During each replication cycle of P. falciparum in the human bloodstream, a small proportion of parasites commits to sexual development and differentiates into transmission-relevant gametocytes. Applying CRISPR-based genome editing, Boltryk et al. engineer P. falciparum lines with sexual commitment rates of 75% to promote future studies on gametocyte biology.
- Sylwia D. Boltryk
- , Armin Passecker
- & Till S. Voss
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Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum
Applying complexome profiling, Evers et al. unravel the composition of mitochondrial oxidative phosphorylation complexes in P. falciparum asexual and sexual blood stages. Abundance of these complexes differs between both stages, supporting the hypothesis that a mitochondrial metabolic switch is central to gametocyte development and functioning.
- Felix Evers
- , Alfredo Cabrera-Orefice
- & Taco W. A. Kooij
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| Open Access
Systematic functional analysis of Leishmania protein kinases identifies regulators of differentiation or survival
Protein kinases are fundamental in cellular signalling required for Leishmania survival throughout the life cycle. Here, Baker and Catta-Preta et al. report on a kinome-wide functional study in Leishmania mexicana to define protein kinases with roles in life cycle transition.
- N. Baker
- , C. M. C. Catta-Preta
- & J. C. Mottram
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Artemisinin-resistant K13 mutations rewire Plasmodium falciparum’s intra-erythrocytic metabolic program to enhance survival
The emergence and spread of artemisinin resistance has compromised antimalarial efficacy. Here, Mok et al. apply quantitative transcriptomics, proteomics, and metabolomics to provide evidence that K13 mutations alter multiple aspects of the parasite’s intra-erythrocytic development to enhance survival following artemisinin treatment.
- Sachel Mok
- , Barbara H. Stokes
- & David A. Fidock
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| Open Access
TgAP2IX-5 is a key transcriptional regulator of the asexual cell cycle division in Toxoplasma gondii
The control of the proper timing of emergence of apicomplexan parasite daughter cells during replication is crucial for their proliferation. Here, Khelifa et al. identify a key transcriptional regulator in the model Apicomplexa Toxoplasma gondii, which regulates the expression of transcription factors necessary for completion of the budding cycle.
- Asma S. Khelifa
- , Cecilia Guillen Sanchez
- & Mathieu Gissot
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| Open Access
Single-cell atlas of the first intra-mammalian developmental stage of the human parasite Schistosoma mansoni
Schistosomes undergo several develepmental stages during infection of humans. Here, the authors perform single-cell RNA sequencing on the earliest intra-mammalian stage of Schistosoma mansoni and generate a comprehensive cell-type atlas for this human parasite.
- Carmen Lidia Diaz Soria
- , Jayhun Lee
- & Matthew Berriman
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| Open Access
Co-option of Plasmodium falciparum PP1 for egress from host erythrocytes
Plasmodium protein phosphatase PP1 is essential for the asexual proliferation of malaria parasites. Here the authors show that PP1 regulates egress of parasites from host red blood cells, integrating parasite intrinsic pathways with environmental signals for release into the bloodstream.
- Aditya S. Paul
- , Alexandra Miliu
- & Manoj T. Duraisingh
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Malaria parasites regulate intra-erythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms
The mechanism underlying periodicity of Plasmodium’s intra-erythrocytic developmental cycle (IDC) is unclear. Here, Subudhi et al. show that serpentine receptor 10 (SR10) plays a role in regulating the schedule of the IDC in line with the timing of host daily rhythms.
- Amit K. Subudhi
- , Aidan J. O’Donnell
- & Arnab Pain
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An intracellular membrane protein GEP1 regulates xanthurenic acid induced gametogenesis of malaria parasites
Mosquito-derived xanthurenic acid (XA) is a trigger for gametogenesis of Plasmodium parasites. Here the authors show that the putative amino acid transporter GEP1 is required for XA-stimulated gametogenesis in Plasmodium yoelii and that it interacts with guanylyl cyclase α (GCα), a cGMP synthesizing enzyme in gametocytes.
- Yuanyuan Jiang
- , Jun Wei
- & Jing Yuan
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| Open Access
Metabolic balancing by miR-276 shapes the mosquito reproductive cycle and Plasmodium falciparum development
Plasmodium growth is adapted to the reproductive cycle of mosquitoes, but underlying mechanisms are unclear. Here, Lampe et al. show that the blood-meal induced miR-276 balances the termination of the mosquito amino acid catabolism and egg development, providing nutrients for Plasmodium sporozoite development.
- Lena Lampe
- , Marius Jentzsch
- & Elena A. Levashina
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Genome-wide real-time in vivo transcriptional dynamics during Plasmodium falciparum blood-stage development
Transcriptomic analysis often doesn’t differentiate between newly synthesized and stabilized mRNAs. Using rapid 4-thiouracil incorporation, Painter et al. here define genome-wide active transcription throughout Plasmodium blood-stage developmental stages and identify associated regulatory DNA sequence motifs.
- Heather J. Painter
- , Neo Christopher Chung
- & Manuel Llinás
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A cryptic cycle in haematopoietic niches promotes initiation of malaria transmission and evasion of chemotherapy
Malaria transmission is effected by intra-erythrocytic parasites that commit to sexual development and form gametocytes. Here, the authors show that early reticulocytes in the major sites of haematopoiesis establish a cryptic asexual cycle; this cycle is characterised by early preferential commitment to gametocytogenesis, which initiates malaria transmission and drug resistance.
- Rebecca S. Lee
- , Andrew P. Waters
- & James M. Brewer
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| Open Access
Dynamic transcriptomes identify biogenic amines and insect-like hormonal regulation for mediating reproduction in Schistosoma japonicum
For reproduction, the human parasiteSchistosoma japonicumrelies on a complex and incompletely understood interplay between female and male schistosomes. Here the authors sequence the transcriptome of female and male schistosomes across eight time points during sexual development.
- Jipeng Wang
- , Ying Yu
- & Wei Hu
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Article
| Open Access
Release of Plasmodium sporozoites requires proteins with histone-fold dimerization domains
Oocyst rupture and release of malaria sporozoites is needed for transmission of parasites from vector to humans. Here the authors identify two proteins, which they name ORP1 and ORP2, that form heterodimers and are required for oocyst rupture.
- Chiara Currà
- , Renate Gessmann
- & Inga Siden-Kiamos
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Cyst-Wall-Protein-1 is fundamental for Golgi-like organelle neogenesis and cyst-wall biosynthesis in Giardia lamblia
Giardia lamblia is a human protozoan parasite with two diploid nuclei, which makes complete knock-out of a gene of interest challenging. Here the authors use a Cre/loxP-based approach to knock-out cyst-wall protein 1 (cwp1) and show that CWP1 is essential for cyst-wall biosynthesis.
- Jacqueline A. Ebneter
- , Sally D. Heusser
- & Carmen Faso
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| Open Access
Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite
The functions of many putative membrane transport proteins of malaria parasites are unknown. Here, Kenthirapalan et al. use mutant strains carrying targeted gene deletions to study the functions of 35 such proteins during the life cycle of Plasmodium bergheiin mosquito and mouse hosts.
- Sanketha Kenthirapalan
- , Andrew P. Waters
- & Taco W. A. Kooij
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| Open Access
Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni
The chronic disease schistosomiasis is caused by the blood flukeSchistosoma mansoni. By studying DNA modifications throughout the lifecycle of the pathogen, the authors identify DNA methylation as a factor in egg development and suggest that the epigenetic machinery responsible may be a therapeutic target.
- Kathrin K. Geyer
- , Carlos M. Rodríguez López
- & Karl F. Hoffmann
Estimating the effects of temperature on transmission of the human malaria parasite, Plasmodium falciparum