Featured
-
-
Article
| Open AccessFar-East Asian Toxoplasma isolates share ancestry with North and South/Central American recombinant lineages
The population genome structure of Asian Toxoplasma remains incompletely understood. This study analyzes intercontinental genomic admixture in 17 isolates from Japan and China, providing insights into the evolution of parasites and their impact on public health.
- Fumiaki Ihara
- , Hisako Kyan
- & Masahiro Yamamoto
-
Article
| Open AccessPersistent and multiclonal malaria parasite dynamics despite extended artemether-lumefantrine treatment in children
Standard diagnostics are often not able to fully capture submicroscopic parasite dynamics after treatment with antimalarials. In this longitudinal analysis of molecular markers of malaria parasitemia in an Ugandan cohort, authors describe persistence of markers following antimalarial therapy with dynamic and complex multiclonal infections in the initial and post-treatment periods.
- Justin Goodwin
- , Richard Kajubi
- & Sunil Parikh
-
Article
| Open AccessA Toxoplasma gondii O-glycosyltransferase that modulates bradyzoite cyst wall rigidity is distinct from host homologues
A Toxoplasma gondii mucin-type O-glycosyltransferase uses a unique catalytic mechanism to modify bradyzoite cyst wall proteins. A second metal coupled to substrate binding is required for catalysis, while an active site glutamate suggests a double-displacement mechanism.
- Pranav Kumar
- , Tadakimi Tomita
- & Nadine L. Samara
-
Article
| Open AccessThe DEAD-box RNA helicase PfDOZI imposes opposing actions on RNA metabolism in Plasmodium falciparum
Min and colleagues study post-transcriptional regulation in the malaria parasite. They describe opposing actions of the DDX6-family RNA helicase complex on the decay and protection of specific mRNA targets during development and stress conditions.
- Hui Min
- , Xiaoying Liang
- & Liwang Cui
-
Article
| Open AccessEstimating the effects of temperature on transmission of the human malaria parasite, Plasmodium falciparum
Malaria transmission is affected by temperature but this relationship is not well characterised. Here, the authors experimentally determine the effect of temperature on parasite development in the mosquito and model how it impacts malaria transmission in Kenya under current and future climate scenarios.
- Eunho Suh
- , Isaac J. Stopard
- & Matthew B. Thomas
-
Article
| Open AccessMetabolic plasticity, essentiality and therapeutic potential of ribose-5-phosphate synthesis in Toxoplasma gondii
Ribose-5-phosphate (R5P) is a precursor for nucleic acid biogenesis. Here, Guo and Ji et al. show that multiple routes can flexibly supply R5P to enable Toxoplasma gondii growth.
- Xuefang Guo
- , Nuo Ji
- & Ningbo Xia
-
Article
| Open AccessDifferentiation 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
-
Article
| Open AccessA commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response
Faecal microbiome transplant has been shown to be able to reduce Clostridioides difficile infection. Here the authors show that an intestinal commensal protozoan reduces C. difficile infection by inhibiting neutrophil recruitment and affecting arginine-ornithine metabolism.
- Huan Yang
- , Xiaoxiao Wu
- & Bing Gu
-
Article
| Open AccessTheileria parasites sequester host eIF5A to escape elimination by host-mediated autophagy
Theileria parasites have evolved mechanisms to evade host cell defenses. Here, Villares et al use an anti-parasite drug to show how intracellular parasites sequester host eIF5A to escape elimination by autophagy pathways.
- Marie Villares
- , Nelly Lourenço
- & Jonathan B. Weitzman
-
Article
| Open AccessMalaria blood stage infection suppresses liver stage infection via host-induced interferons but not hepcidin
Blood and liver stages of malaria parasites can affect each other, but it’s not clear how this may affect live-attenuated whole parasite vaccination. Here the authors show that malaria parasite blood stage infection subdues new infection and vaccination by suppressing growth of its liver stage via host cytokines.
- Hardik Patel
- , Nana K. Minkah
- & Stefan H. I. Kappe
-
Article
| Open AccessGene expression analyses reveal differences in children’s response to malaria according to their age
Here the authors use dual RNA sequencing to characterize host and parasite gene expression from 136 Malian children with symptomatic Plasmodium falciparum infection. They find that parasitemia levels correlate with neutrophil and T cell levels and that the child’s age correlates with innate immune gene expression as well as gametocyte levels.
- Kieran Tebben
- , Salif Yirampo
- & David Serre
-
Article
| Open AccessToxoplasma gondii actin filaments are tuned for rapid disassembly and turnover
Actin is critical to the survival of the parasite Toxoplasma gondii. In this study, Hvorecny and Sladewski et al. show that T. gondii actin forms intrinsically dynamic filaments in vitro due to differences in assembly contacts in the D-loop.
- Kelli L. Hvorecny
- , Thomas E. Sladewski
- & Aoife T. Heaslip
-
Article
| Open AccessDeaggregation of mutant Plasmodium yoelii de-ubiquitinase UBP1 alters MDR1 localization to confer multidrug resistance
Here, the authors show that two mutations in the Plasmodium de-ubiquitinase UBP1 alter the ubiquitination level, membrane localization, and ligand transport direction of multidrug resistance transporter 1 (MDR1), leading to multiple drug resistances.
- Ruixue Xu
- , Lirong Lin
- & Jian Li
-
Article
| Open AccessFlexible and cost-effective genomic surveillance of P. falciparum malaria with targeted nanopore sequencing
Genomic surveillance of Plasmodium falciparum could improve monitoring of drug resistance, but implementation has been hampered due to the large and complex genome. Here, de Cesare et al. develop a flexible and cost-effective nanopore sequencing approach to detect drug resistance and diagnostic escape for P. falciparum malaria.
- Mariateresa de Cesare
- , Mulenga Mwenda
- & Jason A. Hendry
-
Article
| Open AccessProteome-Wide Identification of RNA-dependent proteins and an emerging role for RNAs in Plasmodium falciparum protein complexes
Ribonucleoprotein complexes play fundamental roles in many cellular processes. Here, the authors used a proteome-wide approach, R-DeeP, to identify protein complexes associated with RNA in the deadliest human malaria parasite, Plasmodium falciparum.
- Thomas Hollin
- , Steven Abel
- & Karine G. Le Roch
-
Article
| Open AccessReaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase
New antimalarials are urgently needed. Here, the authors identify Open Source Malaria compound, OSMS-106, as a reaction hijacking inhibitor of the malaria parasite protein synthesis machinery, with potential use for treatment and prophylaxis.
- Stanley C. Xie
- , Yinuo Wang
- & Leann Tilley
-
Article
| Open AccessThe transcription factor AP2XI-2 is a key negative regulator of Toxoplasma gondii merogony
Wang et al. discovered that AP2XI-2 and AP2XII-1 negatively regulate merozoite-primed pre-sexual commitment in Toxoplasma gondii, and parasites depleted of either AP2XI-2 or AP2XII-1 can serve as a valuable in vitro model for studying merogony.
- Jin-Lei Wang
- , Ting-Ting Li
- & Xing-Quan Zhu
-
Article
| Open AccessRevisiting the Plasmodium sporozoite inoculum and elucidating the efficiency with which malaria parasites progress through the mosquito
Using unique single mosquito data the authors revisit the core quantitative relationships between sequential stages of Plasmodium parasites in their vector host. Their findings demonstrate the importance of mosquito parasite burden in onward transmission success.
- Sachie Kanatani
- , Deborah Stiffler
- & Photini Sinnis
-
Article
| Open AccessSustained rhoptry docking and discharge requires Toxoplasma gondii intraconoidal microtubule-associated proteins
The authors identified a series of cytoskeletal proteins involved in the discharge of invasion-related organelles in Toxoplasma gondii. They successfully delineated their functions through the utilization of expansion and cryo-electron microscopy.
- Nicolas Dos Santos Pacheco
- , Albert Tell i Puig
- & Dominique Soldati-Favre
-
Article
| Open AccessMultiple pathways for glucose phosphate transport and utilization support growth of Cryptosporidium parvum
The parasite Cryptosporidium has a reduced genome and is dependent on glycolysis for energy production. Here, Xu et al demonstrate that multiple pathways and glucose transporters exist in this organism which are essential for growth and facilitate energy acquisition and utilization.
- Rui Xu
- , Wandy L. Beatty
- & L. David Sibley
-
Article
| Open AccessVESPA: an optimized protocol for accurate metabarcoding-based characterization of vertebrate eukaryotic endosymbiont and parasite assemblages
DNA sequencing methods for characterizing microbial communities are well developed for bacteria, archaea and fungi, but less so for eukaryotic parasites and commensals. Here, the authors present an optimized and validated metabarcoding protocol for host-associated eukaryotic communities.
- Leah A. Owens
- , Sagan Friant
- & Tony L. Goldberg
-
Article
| Open AccessAntigen recognition reinforces regulatory T cell mediated Leishmania major persistence
Upon skin infection with the parasite Leishmania major, a small group of infected cells remain present in healed skin. Here, Zayats et al. show that regulatory T cells focused towards parasite-derived proteins have strong suppressive capabilities and facilitate parasite persistence in vivo.
- Romaniya Zayats
- , Zhirong Mou
- & Thomas T. Murooka
-
Article
| Open AccessStructures revealing mechanisms of resistance and collateral sensitivity of Plasmodium falciparum to proteasome inhibitors
The proteasome of Plasmodium falciparum (Pf20S) is a promising multi-stage drug target. Using CryoEM Hsu et al. report the structures of parasite and human proteasome in complex with the recently developed inhibitor TDI-8304 to gain insights into its species selectivity.
- Hao-Chi Hsu
- , Daqiang Li
- & Gang Lin
-
Article
| Open AccessAtypical 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
-
Article
| Open AccessAn allele-selective inter-chromosomal protein bridge supports monogenic antigen expression in the African trypanosome
Nuclear organization impacts allelic exclusion. Here, the authors describe a self-limiting protein bridge that connects two chromosomes, and two transcription and splicing compartments, to maintain monogenic VSG expression in the African trypanosome.
- Joana R. C. Faria
- , Michele Tinti
- & David Horn
-
Article
| Open AccessAncient diversity in host-parasite interaction genes in a model parasitic nematode
Host-parasite interactions can lead to negative frequency-dependent selection. Here, the authors sequence the genomes of H. bakeri and H. polygyrus, parasites of house and wood mice, respectively, and find that proteins that interact with the host immune response are often highly diverse.
- Lewis Stevens
- , Isaac Martínez-Ugalde
- & Mark Blaxter
-
Article
| Open AccessCytolytic circumsporozoite-specific memory CD4+ T cell clones are expanded during Plasmodium falciparum infection
It is important to understand why some individuals in endemic regions acquire natural immunity against malaria while others remain susceptible. Here authors show that during episodes of Plasmodium falciparum malaria, circumsporozoite-specific cytolytic memory CD4+ T cells are clonally expanded in patients, and those with clinical immunity demonstrate reduction in the chemotactic and inhibitory receptor expression in ZEB2+ memory CD4+ T cells.
- Raquel Furtado
- , Mahinder Paul
- & Grégoire Lauvau
-
Article
| Open Access3D reconstructions of parasite development and the intracellular niche of the microsporidian pathogen Encephalitozoon intestinalis
Microsporidia are obligate intracellular parasitic fungi that can cause opportunistic infections in humans. Here, Antao et al. investigate the intracellular life cycle of human-infecting Encephalitozoon intestinalis using serial block-face scanning electron microscopy to characterize parasite organelle development and host-cell mitochondrial remodeling.
- Noelle V. Antao
- , Cherry Lam
- & Gira Bhabha
-
Article
| Open AccessVector-borne Trypanosoma brucei parasites develop in artificial human skin and persist as skin tissue forms
Here, authors show that tsetse-fly transmitted trypanosomes rapidly differentiate within human skin equivalents, eventually entering a reversible quiescent stage and conclude that these skin tissue forms may contribute to long-term parasite infections in asymptomatic individuals.
- Christian Reuter
- , Laura Hauf
- & Markus Engstler
-
Article
| Open AccessA single pseudouridine on rRNA regulates ribosome structure and function in the mammalian parasite Trypanosoma brucei
Trypanosomes are the causative agent of sleeping sickness. Here the authors demonstrate that the loss of single pseudouridine in ribosomal RNA affects the stoichiometry of ribosomal proteins and translation of a subset of proteins.
- K. Shanmugha Rajan
- , Hava Madmoni
- & Shulamit Michaeli
-
Article
| Open AccessSingle cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets
The use of single cell sequencing has enabled more detailed analysis of the immune response to infection. Here the authors characterise the immune response to malaria infection in an endemic region using single cell transcriptomics indicating regulatory signatures associated with infection.
- Nicholas L. Dooley
- , Tinashe G. Chabikwa
- & Michelle J. Boyle
-
Article
| Open AccessEncystation 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
-
Article
| Open AccessHOP1 and HAP2 are conserved components of the meiosis-related machinery required for successful mating in Leishmania
Genetic exchange has been experimentally demonstrated for Leishmania during sand fly development, indicating a meiotic mechanism. Here the authors show that meiosis-related genes HOP1 and HAP2-2 are essential for Leishmania hybridization in vitro and in sand flies and that their deletion in one or both parents hinders mating competence.
- Carolina Moura Costa Catta-Preta
- , Tiago Rodrigues Ferreira
- & David Sacks
-
Article
| Open AccessIL-17 signalling is critical for controlling subcutaneous adipose tissue dynamics and parasite burden during chronic murine Trypanosoma brucei infection
Trypanosome brucei is known to colonise the subcutaneous white adipose tissue and the interaction with the cellular locale could play key roles in pathogenesis and host response. Here the author’s use single cell approaches and in vivo animal models, and show a role for IL-17 in the adipose tissue response and parasite burden in a chronic murine model of infection.
- Matthew C. Sinton
- , Praveena R. G. Chandrasegaran
- & Juan F. Quintana
-
Article
| Open AccessMultiple parallel origins of parasitic Marine Alveolates
The Marine Alveolates (MALVs) include important parasites of other protists/animals. Here, using new data from MALV-I, the psammosids, and a new group called the eleftherids, the authors show MALVs, and therefore parasitism in early dinoflagellates, evolved from two distinct free-living ancestors.
- Corey C. Holt
- , Elisabeth Hehenberger
- & Patrick J. Keeling
-
Article
| Open AccessProduction of leishmanin skin test antigen from Leishmania donovani for future reintroduction in the field
As leishmaniasis control programs and new vaccines are advancing, it is necessary to re-introduce the leishmanin skin test to monitor transmission and immunity. This study describes the generation and validation of a new leishmanin skin test antigen for future re-introduction into endemic countries.
- Ranadhir Dey
- , Jalal Alshaweesh
- & Greg Matlashewski
-
Article
| Open AccessLocalized cardiac small molecule trajectories and persistent chemical sequelae in experimental Chagas disease
The impact of antiparasitic treatment on local tissue responses in the case of chronic Chagas disease (caused by Trypanosoma cruzi infection) is not well understood. Authors provide insight into clinical treatment failure and drivers of post-infectious conditions.
- Zongyuan Liu
- , Rebecca Ulrich vonBargen
- & Laura-Isobel McCall
-
Article
| Open AccessGut Bacteroides act in a microbial consortium to cause susceptibility to severe malaria
Specific gut microbiota constituents that affect the severity of malaria are unknown. Here, Mandal et al. identify specific Bacteroides species causing susceptibility to severe malaria in mice and correlate with the severity of malaria in Ugandan children.
- Rabindra K. Mandal
- , Anita Mandal
- & Nathan W. Schmidt
-
Article
| Open AccessExtracellular vesicles could be a putative posttranscriptional regulatory mechanism that shapes intracellular RNA levels in Plasmodium falciparum
Here, Kioko et al. describe a putative posttranscriptional RNA regulation mechanism involving secreted extracellular vesicles to maintain the intracellular steady-state RNA levels during the asexual blood stage of malaria parasites.
- Mwikali Kioko
- , Alena Pance
- & Abdirahman I. Abdi
-
Article
| Open AccessThe parasitic nematode Strongyloides ratti exists predominantly as populations of long-lived asexual lineages
Nematodes are important parasites of people and animals. Here, the authors study the population structure of a nematode parasite of wild rats finding that it consists of mixtures of mainly asexual lineages widely dispersed across the host population.
- Rebecca Cole
- , Nancy Holroyd
- & Mark Viney
-
Article
| Open AccessClinically relevant atovaquone-resistant human malaria parasites fail to transmit by mosquito
Malaria parasites from patients who fail atovaquone therapies are highly drug-resistant, with mutations at Y268 in cytochrome b. Here the authors show that this mutation results in multiple defects in the parasite’s development and prevents transmission from mosquitoes to mice.
- Victoria A. Balta
- , Deborah Stiffler
- & Theresa A. Shapiro
-
Article
| Open AccessCryo-electron microscopy of IgM-VAR2CSA complex reveals IgM inhibits binding of Plasmodium falciparum to Chondroitin Sulfate A
Placental malaria parasite binds to host IgM however its functional importance was not understood. Here, authors resolved structure of IgM-VAR2CSA complex using cryo-EM to show that IgM masks VAR2CSA and inhibits its binding to receptor.
- Reetesh Raj Akhouri
- , Suchi Goel
- & Ulf Skoglund
-
Article
| Open AccessA transcriptional network required for bradyzoite development in Toxoplasma gondii is dispensable for recrudescent disease
Toxoplasma gondii can develop into dormant bradyzoites that persist in tissue and can be reactivated. Here the authors identify an RNA binding protein that they call Regulator of Cystogenesis 1 (ROCY1), and show that it is required for bradyzoite development in vitro and in vivo but is not required for long term persistence of parasites that reactivate in a mouse model of recrudescence.
- Sarah L. Sokol-Borrelli
- , Sarah M. Reilly
- & Jon P. Boyle
-
Article
| Open AccessStructure guided mimicry of an essential P. falciparum receptor-ligand complex enhances cross neutralizing antibodies
The AMA1-RON2 complex is important for Plasmodium falciparum invasion and a potential vaccine target. Here the authors engineer a fusion protein of AMA1 and RON2 loop that mimics the receptor-ligand complex and show that it induces antibodies that neutralize non-vaccine type parasites.
- Sean Yanik
- , Varsha Venkatesh
- & Prakash Srinivasan
-
Article
| Open AccessEstimating the burden of severe malarial anaemia and access to hospital care in East Africa
Severe malarial anaemia is a clinical manifestation of severe malaria, with the burden highly concentrated in children. In this work, authors statistically model household survey and in-hospital data to estimate the proportion of severe malarial anaemia cases that access hospital care.
- Peter Winskill
- , Aggrey Dhabangi
- & Lucy C. Okell
-
Article
| Open AccessThe structure of a Plasmodium vivax Tryptophan Rich Antigen domain suggests a lipid binding function for a pan-Plasmodium multi-gene family
Although the precise function of Tryptophan rich antigen multi-gene family (TRAgs) proteins is not known in any Plasmodium species several members of the P. vivax TRAg family have been reported to have red blood cell binding properties. Here, Kundu and Naskar et al. provide the X-ray crystallography structure of a P. vivax TRAg domain of PVP01_0000100. Structural and biochemical assays suggest a lipid binding function for a pan-Plasmodium multi-gene family.
- Prasun Kundu
- , Deboki Naskar
- & Julian C. Rayner
-
Article
| Open AccessPlasmodium ARK2 and EB1 drive unconventional spindle dynamics, during chromosome segregation in sexual transmission stages
The Aurora kinases orchestrate chromosome segregation and cell division. Zeeshan et al. studied divergent Plasmodium ARK2 and EB1 using live cell imaging, proteomics and functional genetics. These are critical components for atypical spindle dynamics during transmission stages.
- Mohammad Zeeshan
- , Edward Rea
- & Rita Tewari
-
Article
| Open Accessγδ T cells control murine skin inflammation and subcutaneous adipose wasting during chronic Trypanosoma brucei infection
Trypansome brucei infection can result in colonisation of the skin but how this impacts the skin architecture and immune response has not been fully resolved. Here the authors apply a spatially resolved single cell transcriptomics approach in a murine model of infection, and suggest a role for IL-17- producing γδ T cells in the immune response to T. brucei skin infection.
- Juan F. Quintana
- , Matthew C. Sinton
- & Annette MacLeod
-
Article
| Open AccessFAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction
Microtubule inner proteins (MIPs) contribute to species-specific motility characteristics but are largely unstudied. Here, the authors combine functional, structural and proteomic analysis in T. brucei to advance fundamental understanding of MIP assembly and identify trypanosome-specific MIPs required for motility.
- Michelle M. Shimogawa
- , Angeline S. Wijono
- & Kent L. Hill