Parasitology articles within Nature Communications

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  • Article
    | Open Access

    Trypanosomes evade the immune response through antigenic variation of a surface coat containing variant surface glycoproteins (VSG). They also express invariant surface glycoproteins (ISGs), which are less well understood. Here, Macleod et al. show that ISG65 of T. brucei is a receptor for complement component 3. They provide the crystal structure of T. brucei ISG65 in complex with complement C3d and show evidence that ISG65 is involved in reducing trypanosome susceptibility to C3-mediated clearance in vivo.

    • Olivia J. S. Macleod
    • , Alexander D. Cook
    •  & Mark Carrington

  • Article
    | Open Access

    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

  • Article
    | Open Access

    The basal complex is orchestrating Toxoplasma gondii cell division steps. Here, the authors use proximity biotinylation to map the proteome of this contractile ring, identify components acting on its formation, stability and constriction, and reveal bidirectional daughter budding.

    • Klemens Engelberg
    • , Tyler Bechtel
    •  & Marc-Jan Gubbels

  • Article
    | Open Access

    Toxoplasma gondii can persist in neurons in the central nervous system, presumably because neurons have limited cell-intrinsic immune responses. However, here, Chandrasekaran et al. show that IFN-gamma stimulated primary murine neurons can clear T. gondii and that IFN-gamma stimulated murine and human neurons show decreased infection rates.

    • Sambamurthy Chandrasekaran
    • , Joshua A. Kochanowsky
    •  & Anita A. Koshy

  • Article
    | Open Access

    Egress of Plasmodium from host erythrocytes is mediated by effector proteins. Aspartic protease plasmepsin X (PM X) regulates the activity for many of these effectors, is essential for replication and is a promising drug target. Here, Mukherjee et al. map the self-cleavage sites of PM X, show that the N-terminal part of its prodomain is required for intracellular trafficking and correlate the maturation and subcellular activity of PM X in microneme, exoneme and rhoptry organelle function.

    • Sumit Mukherjee
    • , Suong Nguyen
    •  & Daniel E. Goldberg

  • Article
    | Open Access

    Here, Lopaticki et al. show that Plasmodium falciparum expresses a Dpy19 C-mannosyltransferase in the endoplasmic reticulum that glycosylates TSR domains. Functional characterization shows that PfDpy19 plays a critical role in transmission through mosquitoes as PfDpy19-deficiency abolishes C-glycosylation and destabilizes proteins relevant for gametogenesis and oocyst formation.

    • Sash Lopaticki
    • , Robyn McConville
    •  & Justin A. Boddey

  • Article
    | Open Access

    Plasmodium vivax is the most widespread human malaria parasite but due to its tropism for immature red blood cells in vitro culturing and studies are difficult. Here, LuizaBatista et al. generate a humanized mouse supporting human erythropoiesis and allowing asexual and sexual development of P. vivax in bone marrow and peripheral blood, as well as transmission to mosquitoes.

    • Camilla Luiza-Batista
    • , Sabine Thiberge
    •  & Sylvie Garcia

  • Article
    | Open Access

    Encystment is a process that allows free-living and parasitic amoebae to survive in unfavorable environments. Here, Bernard et al. provide detailed insights into the early stages of encystment of Acanthamoeba castellanii by integrating RNA-Seq, proteomics and phosphoproteomics data sets.

    • Clément Bernard
    • , Marie Locard-Paulet
    •  & Ascel Samba-Louaka

  • Article
    | Open Access

    Intrinsically disordered proteins (IDP) are pleotropic proteins with diverse functions. Here the authors show that an IDP, TgIST, from T. gondii blocks interferon-induced gene expression by binding to the STAT1 dimer interface and preventing the recruitment of co-transcriptional activators, CBP/p300, to STAT1 to inhibit expression of immunity genes.

    • Zhou Huang
    • , Hejun Liu
    •  & L. David Sibley

  • Article
    | Open Access

    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

  • Article
    | Open Access

    Leishmania use large (5–10 kb) transcriptional start regions, where the chromatin is highly enriched for acetylated histones, to drive the expression of polycistronic gene arrays. Here the authors show bromodomain-containing protein BDF5 is enriched at transcriptional start sites and its depletion leads to cell death in vitro and in murine infections, and they identify its interactors.

    • Nathaniel G. Jones
    • , Vincent Geoghegan
    •  & Jeremy C. Mottram

  • Article
    | Open Access

    During the erythrocyte (RBC) stage of P. falciparum infection variant surface antigens (VSAs) such as PfEMP1s and RIFINs expressed on RBCs are important for infection and evasion of host innate immune system. Here, Chew et al. use a NSG mouse model, which is deficient in B, T and NK cells but retains macrophages, to show that PfEMP1 surface expression is required for in vivo adaptation as well as in vitro evasion of macrophage phagocytosis.

    • Marvin Chew
    • , Weijian Ye
    •  & Peter Preiser

  • Article
    | Open Access

    The whipworm Trichuris trichiura is a soil-transmitted helminth that causes the neglected tropical disease trichuriasis in humans. Here, the authors produce whole genome sequences of modern and ancient samples from humans and non-human primates to characterise the genomic diversity and evolution of this pathogen.

    • Stephen R. Doyle
    • , Martin Jensen Søe
    •  & Christian Moliin Outzen Kapel

  • Article
    | Open Access

    The reasons why malaria manifests with a variety of well-recognized clinical phenotypes remain poorly understood. Here, using distinct rodent models, the authors reveal that the microbiota colonizing the lung promotes respiratory distress syndrome and mortality during malaria infections.

    • Debanjan Mukherjee
    • , Ângelo Ferreira Chora
    •  & Maria M. Mota

  • Article
    | Open Access

    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

  • Article
    | Open Access

    Circumsporozoite protein (CSP), the major surface protein of Plasmodium sporozoites, is important for parasite targeting to mosquito salivary glands and the mammalian liver. Here, Zhu et al. show that CSP is required for rodent malaria oocysts to evade mosquito immunity by inducing hemocyte nitration and causing subsequent defects in sporozoite-release from oocysts.

    • Feng Zhu
    • , Hong Zheng
    •  & Wenyue Xu

  • Article
    | Open Access

    Mitochondria import most of their proteins posttranslationally. Here, Dewar et al. characterize the mitochondrial quality control mechanism of Trypanosoma brucei. Through proteomics and functional studies, they show that only ablation of ATOM69, one of the seven subunits of its mitochondrial protein translocase, triggers a unique quality control pathway resulting in TbUbL1 release from the nucleus and subsequent proteasomal degradation of non-imported mitochondrial proteins.

    • Caroline E. Dewar
    • , Silke Oeljeklaus
    •  & André Schneider

  • Article
    | Open Access

    Genetically identical cells can be phenotypically diverse to allow adaptive flexibility in a given environment. This phenotypic diversity is driven by epigenetic and transcriptional variability. Here, Tripathi et al. perform scRNA-seq of isogenic and non-isogenic Plasmodium falciparum schizont populations to explore transcriptional heterogeneity and stochastic gene expression during the course of development.

    • Jaishree Tripathi
    • , Lei Zhu
    •  & Zbynek Bozdech

  • Article
    | Open Access

    Plasmodium gametes and sporozoites activate surface-bound plasminogen to plasmin that degrades extracellular matrix barriers, therewith facilitating parasite motility in mosquitoes and mammalian hosts. To control malaria transmission, Pascini et al. generate Anopheles stephensi transgenic mosquitoes constitutively secreting human plasminogen activator inhibitor 1 in midgut and/or saliva which leads to inhibition of plasminogen activation and a reduction in oocyst intensity, infection prevalence, and transmission.

    • Tales V. Pascini
    • , Yeong Je Jeong
    •  & Joel Vega-Rodríguez

  • Comment
    | Open Access

    Studying malaria transmission biology using scRNA-sequencing provides information on within-host strain diversity and transcriptional states. Here, we comment on our collaborative efforts at establishing single-cell capacities in sub-Saharan Africa and the challenges encountered in Mali’s endemic setting.

    • Antoine Dara
    • , Sunil Kumar Dogga
    •  & Mara K. N. Lawniczak

  • Comment
    | Open Access

    Economic evaluations of public health interventions to prevent malaria should consider the adoption of wider perspectives and the inclusion of non-health impacts, particularly economic development outcomes, such as education. This is especially relevant in malaria elimination settings and in the context of the current SARS-CoV-2 pandemic.

    • Elisa Sicuri
    • , Francesco Ramponi
    •  & Francisco Saúte

  • Comment
    | Open Access

    Malaria cases and deaths remain unacceptably high and are resurgent in several settings, though recent developments inspire optimism. This includes the approval of the world’s first malaria vaccine and results from novel vaccine candidates and trials testing innovative combinatorial interventions.

    • Prasanna Jagannathan
    •  & Abel Kakuru

  • Article
    | Open Access

    Plasmodium malariae is a cause of malaria in humans and related species have been identified in non-human primates. Here, the authors use genomic analyses to establish that human P. malariae arose from a host switch of an ape parasite whilst a species infecting New World monkeys can be traced to a reverse zoonosis.

    • Lindsey J. Plenderleith
    • , Weimin Liu
    •  & Paul M. Sharp

  • Article
    | Open Access

    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

  • Article
    | Open Access

    The function of RNA-binding domain abundant in Apicomplexans (RAP) protein family members is largely unknown. Here, using high-throughput functional genomics, including metabolomics, Hollin et al. characterize two RAP proteins that are essential for Plasmodium falciparum survival and control mitochondrial rRNAs.

    • Thomas Hollin
    • , Steven Abel
    •  & Karine G. Le Roch

  • Article
    | Open Access

    The snail Bulinus truncatus is an intermediate host of the carcinogenic human blood fluke Schistosoma haematobium. Here the authors report the genome of Bu. truncatus, explore protein groups inferred to play a role in its interaction with the schistosome parasite, and identify expansions in gene families linked to immune response regulation.

    • Neil D. Young
    • , Andreas J. Stroehlein
    •  & Robin B. Gasser

  • Article
    | Open Access

    Antibodies can have synergistic effects, but mechanisms are not well understood. Here, Ragotte et al. identify three antibodies that bind neighbouring epitopes on CyRPA, a malaria vaccine candidate, and show that lateral interactions between the antibodies slow dissociation and inhibit parasite growth synergistically.

    • Robert J. Ragotte
    • , David Pulido
    •  & Simon J. Draper

  • Article
    | Open Access

    Release of genetically-modified sterile mosquitoes is a potential method of malaria control but has yet to be tested in the field. Here, the authors perform a mark-release-recapture experiment and show that genetically-modified mosquitoes have reduced survival and dispersal compared to wild-types.

    • Franck Adama Yao
    • , Abdoul-Azize Millogo
    •  & Abdoulaye Diabaté

  • Article
    | Open Access

    African trypanosomes collectively move in a process called social motility. Here, the authors show that procyclic forms acidify their environment as a consequence of glucose metabolism, generating pH gradients by diffusion that are sensed via cyclic AMP signalling. Parasite mutants defective in cAMP signaling are inhibited in fly infection.

    • Sebastian Shaw
    • , Sebastian Knüsel
    •  & Isabel Roditi

  • Article
    | Open Access

    Coenzyme A (CoA) is an essential metabolite found in all organisms and its synthesis involves five conserved enzymatic steps and uses pantothenate (Pan) as a precursor. Here, Lunghi et al. examine the Pan synthesis pathway in Toxoplasma gondii and find that Pan is crucial for the establishment of chronic but not acute infection.

    • Matteo Lunghi
    • , Joachim Kloehn
    •  & Dominique Soldati-Favre

  • Article
    | Open Access

    A Variant Surface Glycoprotein (VSG) coat protects bloodstream form T. brucei. Applying super-resolution microscopy Budzak et al. characterize a set of nuclear bodies, which associate with the active expression site in bloodstream form T. brucei and highlight the importance of trans-splicing for transcription of VSG.

    • James Budzak
    • , Robert Jones
    •  & Gloria Rudenko

  • Article
    | Open Access

    After transmission of Plasmodium sporozoites from infected mosquitoes, parasites first infect hepatocytes. Here, Cha et al. identify a sporozoite ligand (phospholipid scramblase) and the hepatocytic receptor (carbamoyl-phosphate synthetase 1) as relevant for hepatocyte invasion and show that an antibody to hepatocyte-binding peptide 1 (HP1), which structurally mimics the sporozoite ligand, partially protects mice from infection.

    • Sung-Jae Cha
    • , Min-Sik Kim
    •  & Marcelo Jacobs-Lorena

  • Article
    | Open Access

    Micronutrient supplements are key to global efforts to address child malnutrition. Here, in a cohort of children, previously enrolled into a large cluster randomized controlled trial of micronutrient supplementation in Pakistan, Popovic et al. find that vitamins and iron increase carriage of protozoa and fungi in the gut, potentially disrupting the bacterial microbiome.

    • Ana Popovic
    • , Celine Bourdon
    •  & Lisa G. Pell

  • Article
    | Open Access

    To date there is only one single drug with modest efficacy and no vaccine available to protect from schistosomiasis. Here, Amaral et al. characterize the self-cure process of rhesus macaques following primary infection and secondary challenge with Schistosoma mansoni to inform future vaccine development studies.

    • Murilo Sena Amaral
    • , Daisy Woellner Santos
    •  & Sergio Verjovski-Almeida

  • Article
    | Open Access

    Two-pore channels (TPCs) are cation channels that localize to acidic organelles to regulate Ca2+ dependent events. Here, Li et al. characterize a TPC from Toxoplasma gondii(TgTPC) that localizes to the apicoplast, is critical for maintaining its integrity and relevant for Ca2+ uptake from the ER through stabilizing inter-organelle contact.

    • Zhu-Hong Li
    • , Thayer P. King
    •  & Silvia N. J. Moreno

  • Article
    | Open Access

    Trypanosoma brucei undergoes developmental steps during host infection. Here, using oligopeptide-induced differentiation in vitro, authors model replicative ‘slender’ to transmissible ‘stumpy’ bloodstream forms and identify developmental and cell cycle regulators by single cell transcriptomics.

    • Emma M. Briggs
    • , Federico Rojas
    •  & Thomas D. Otto

  • Article
    | Open Access

    The rhoptry is an apical secretory organelle of apicomplexan parasites that is essential for host cell invasion. Here, Mageswaran et al. provide in situ ultrastructures of rhoptries from two pathogens, revealing a conserved architecture including luminal filaments and a distinct docking mechanism.

    • Shrawan Kumar Mageswaran
    • , Amandine Guérin
    •  & Yi-Wei Chang

  • Article
    | Open Access

    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

  • Article
    | Open Access

    Schistosomiasis control strategies rely on mass drug administration (MDA) using praziquantel. Here, Berger et al. perform whole-genome sequencing of larvae from infected children across Ugandan regions with differing MDA histories. They find extensive gene flow with limited positive selection suggesting minimal change post MDA.

    • Duncan J. Berger
    • , Thomas Crellen
    •  & James A. Cotton

  • Article
    | Open Access

    To understand malaria symptoms, several studies investigate association between parasite’s transcriptome and disease severity. Here, Thomson-Luque et al. reanalyze available transcriptomic data of P. falciparum and find that longer circulation of infected erythrocytes without sequestering to endothelial cells associates with decreasing parasitaemia and less severe disease.

    • Richard Thomson-Luque
    • , Lasse Votborg-Novél
    •  & Silvia Portugal

  • Article
    | Open Access

    Repeating fever is a hallmark of malaria. Here, a large-scale forward genetic screen in malaria-causing Plasmodium falciparum identifies genes associated with parasite tolerance to host fever, including apicoplast targeted isoprenoid biosynthesis—sharing features with artemisinin resistance.

    • Min Zhang
    • , Chengqi Wang
    •  & John H. Adams

  • Article
    | Open Access

    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

  • Article
    | Open Access

    Host cell invasion by Toxoplasma gondii depends on the heavily phosphorylated RON complex, but the relevance and regulation of these modifications are not understood. Here, the authors identify the kinase RON13 as a key virulence factor, determine its structure and show that it phosphorylates the RON complex.

    • Gaëlle Lentini
    • , Rouaa Ben Chaabene
    •  & Dominique Soldati-Favre

  • Article
    | Open Access

    Here, Geoghegan, Evelyn et al. provide a lattice light-sheet microscopy based 4D imaging pipeline to quantitatively investigate Plasmodium spp. invasion and show that the nascent parasitophorous vacuole is predominantly formed from host’s erythrocyte membrane and undergoes continuous remodeling throughout invasion.

    • Niall D. Geoghegan
    • , Cindy Evelyn
    •  & Kelly L. Rogers

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