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| Open AccessMultiplexed ddPCR-amplicon sequencing reveals isolated Plasmodium falciparum populations amenable to local elimination in Zanzibar, Tanzania
Sequencing malaria parasites from low density infections in small amounts of dried blood is important for large-scale genomic surveillance. Here, the authors develop and validate a highly multiplexed droplet digital PCR-based amplicon deep sequencing assay and apply it to data from Zanzibar, Tanzania.
- Aurel Holzschuh
- , Anita Lerch
- & Cristian Koepfli
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Article
| Open AccessGeneration of a mutator parasite to drive resistome discovery in Plasmodium falciparum
The ability to evolve Plasmodium drug resistance in vitro is challenging and time consuming. Here, Kümpornsin et al. generated a Plasmodium falciparum parasite line with an elevated mutation rate by impairing the proof-reading activity of DNA polymerase, which results in a higher mutation rate, quick resistance development, and a lower inoculum than wild type to support the identification of new antimalarial targets and understand drug resistance mechanisms.
- Krittikorn Kümpornsin
- , Theerarat Kochakarn
- & Marcus C. S. Lee
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| Open AccessDecreased susceptibility of Plasmodium falciparum to both dihydroartemisinin and lumefantrine in northern Uganda
In this work, susceptibilities to two key antimalarials, dihydroartemisinin and lumefantrine, were associated with multiple genetic polymorphisms in Plasmodium falciparum, and were lower in northern Uganda, where resistance-mediating mutations have emerged, compared to eastern Uganda.
- Patrick K. Tumwebaze
- , Melissa D. Conrad
- & Philip J. Rosenthal
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| Open AccessGenome-wide functional screening of drug-resistance genes in Plasmodium falciparum
Plasmodium falciparum malaria is treated using artemisinin combination therapy (ACT), in which artemisinin is supplied along with partner drugs such as mefloquine, piperaquine, and lumefantrine. However, resistance has been reported in endemic regions. To identifying new effector genes involved in resistance, Iwanaga et al. develop a large scale transgenic screen with genomic libraries of resistance strains. Using this approach they provide evidence that transcriptional upregulation of pfmdr7 contributes to mefloquine resistance in a clinical isolate.
- Shiroh Iwanaga
- , Rie Kubota
- & Chairat Uthaipibull
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Article
| Open AccessA unique Toxoplasma gondii haplotype accompanied the global expansion of cats
Toxoplasma gondii can infect all warm-blooded animals, with felidae being the definitive hosts. Despite this broad host range, most clinical and animal isolates belong to few clonal lineages. Here, Galal et al. perform whole-genome sequencing of isolates from distinct geographical regions and estimate T. gondii mutation rate and generation time. They find that recent waves of migration disseminated the parasite from Old to New World and identify a unique haplotype that likely accompanied the global expansion of cats and is today common to all intercontinental lineages and hybrid populations.
- Lokman Galal
- , Frédéric Ariey
- & Aurélien Mercier
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| Open AccessGenome-scale RNA interference profiling of Trypanosoma brucei cell cycle progression defects
Progression of the canonical eukaryotic cell cycle is tightly regulated. While the cell cycle control of flagellated protozoa Trypanosoma brucei shares conserved features with other eukaryotes certain cell cycle checkpoints are absent. Here, Marques et al. provide a genome-scale RNAi screen followed by sorting of parasites according to their cell cycle stage to inform about cell cycle regulators of bloodstream T. brucei.
- Catarina A. Marques
- , Melanie Ridgway
- & David Horn
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Article
| Open AccessPopulation genomics of ancient and modern Trichuris trichiura
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
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| Open AccessStochastic expression of invasion genes in Plasmodium falciparum schizonts
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
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Comment
| Open AccessTackling malaria transmission at a single cell level in an endemic setting in sub-Saharan Africa
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
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Article
| Open AccessZoonotic origin of the human malaria parasite Plasmodium malariae from African apes
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
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| Open AccessNuclear genome of Bulinus truncatus, an intermediate host of the carcinogenic human blood fluke Schistosoma haematobium
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
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| Open AccessWhole-genome sequencing of Schistosoma mansoni reveals extensive diversity with limited selection despite mass drug administration
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
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| Open AccessThe apicoplast link to fever-survival and artemisinin-resistance in the malaria parasite
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
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Article
| Open AccessTgAP2IX-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 AccessThe transcriptome of circulating sexually committed Plasmodium falciparum ring stage parasites forecasts malaria transmission potential
Malaria gametocytes are sexual-stage parasites transmitted from mammalian host’s blood back to their insect vector. Here, Prajapati et al. identify gametocyte-committed ring-stage biomarkers allowing to forecast malaria transmission potential.
- Surendra K. Prajapati
- , Ruth Ayanful-Torgby
- & Kim C. Williamson
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Article
| Open AccessGenetic screens reveal a central role for heme metabolism in artemisinin susceptibility
Artemisinin (ART) resistance poses a problem for malaria elimination. Here, the authors perform genome-wide CRISPR screens in Toxoplasma gondii and identify that the putative transporter Tmem14c and mitochondrial heme metabolism, through mitochondrial protease DegP2, affect ART susceptibility.
- Clare R. Harding
- , Saima M. Sidik
- & Sebastian Lourido
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| Open AccessEntamoeba and Giardia parasites implicated as hosts of CRESS viruses
Metagenomics allows virus genome discovery, but the viral hosts are often not identified. Here, Kinsella et al. use recombination events between virus genomes, statistical association of viruses to hosts in clinical samples, and analysis of endogenous viral elements in host genomes to identify probable hosts of three CRESS virus families.
- Cormac M. Kinsella
- , Aldert Bart
- & Lia van der Hoek
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Article
| Open AccessSex chromosome evolution in parasitic nematodes of humans
Many nematode worms, including Caenorhabditis elegans have XX/XO sex determination, while other species have XY. The authors use a new genome assembly of the filarial parasite Brugia malayi and published data to show that nematode sex chromosome evolution is highly plastic.
- Jeremy M. Foster
- , Alexandra Grote
- & Elodie Ghedin
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| Open AccessDistinct roles for H4 and H2A.Z acetylation in RNA transcription in African trypanosomes
Histone modification and deposition are key regulators of transcription. Here, Kraus et al. provide a quantitative histone acetylome for Trypanosoma brucei, identify histone modifications enriched at transcription start sites, and show how H4 and H2A.Z acetylation affect histone deposition and transcription in trypanosomes.
- Amelie J. Kraus
- , Jens T. Vanselow
- & T. Nicolai Siegel
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Article
| Open AccessVariant antigen diversity in Trypanosoma vivax is not driven by recombination
Trypanosoma rely on variant surface glycoprotein (VSG) to escape host immunity, but mechanisms generating antigenic diversity of VSG are poorly understood. Here, Silva-Pereira et al. show that T. vivax has a limited antigenic repertoire compared to T. brucei and that recombination plays little role in diversifying T. vivax VSG sequences.
- Sara Silva Pereira
- , Kayo J. G. de Almeida Castilho Neto
- & Andrew P. Jackson
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Article
| Open AccessCoupling chemical mutagenesis to next generation sequencing for the identification of drug resistance mutations in Leishmania
Here, Bhattacharya et al. chemically mutagenize Leishmania and identify genes associated with resistance to miltefosine and paromomycin by next generation sequencing. The study shows that a protein kinase (CDPK1) can mediate resistance to paromomycin by affecting translation.
- Arijit Bhattacharya
- , Philippe Leprohon
- & Marc Ouellette
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| Open AccessHigh-resolution micro-epidemiology of parasite spatial and temporal dynamics in a high malaria transmission setting in Kenya
Here, Nelson et al. use amplicon next-generation sequencing of two P. falciparum polymorphic gene regions to investigate the genetic similarity of parasite populations across time and space in a pediatric cohort in Kenya. They identify both micro- and macro-scale structuring of malaria parasites in this high-transmission setting, which could inform future intervention strategies.
- Cody S. Nelson
- , Kelsey M. Sumner
- & Wendy P. O’Meara
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Article
| Open AccessMeiotic sex in Chagas disease parasite Trypanosoma cruzi
Here, Llewellyn and colleagues present evidence of meiotic sex in Trypanosoma cruzi, the causative agent of Chagas disease. These findings have implications for the epidemiology of the disease in endemic regions and challenge existing ideas that the parasites are strictly clonal.
- Philipp Schwabl
- , Hideo Imamura
- & Martin S. Llewellyn
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| Open AccessGenomic structure and diversity of Plasmodium falciparum in Southeast Asia reveal recent parasite migration patterns
Understanding genomic variation in Plasmodium falciparum parasites and inferring migration patterns can guide malaria elimination strategies. Using genome-wide data for 1722 parasites collected from 54 districts, the authors use identity-by-descent approaches to estimate regional parasite migration and spread of artemisinin drug resistance.
- Amol C. Shetty
- , Christopher G. Jacob
- & Marie A. Onyamboko
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| Open AccessThe origins of malaria artemisinin resistance defined by a genetic and transcriptomic background
Mechanisms underlying increasing artemisinin resistance of Plasmodium in Southeast Asia remain unclear. Here, Zhu et al. integrate TWAS, GWAS and eQTL analyses for 773 P. falciparum isolates and identify genetic and transcriptomic backgrounds to artemisinin resistance.
- Lei Zhu
- , Jaishree Tripathi
- & Ye Htut
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| Open AccessEmerging Southeast Asian PfCRT mutations confer Plasmodium falciparum resistance to the first-line antimalarial piperaquine
Increasing resistance of Plasmodium falciparum strains to piperaquine (PPQ) in Southeast Asia is of concern and resistance mechanisms are incompletely understood. Here, Ross et al. show that mutations in the P. falciparum chloroquine resistance transporter are rapidly increasing in prevalence in Cambodia and confer resistance to PPQ.
- Leila S. Ross
- , Satish K. Dhingra
- & David A. Fidock
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| Open AccessGenomic analysis of a pre-elimination Malaysian Plasmodium vivax population reveals selective pressures and changing transmission dynamics
Plasmodium vivax incidence in Malaysia has declined markedly over the last decade, despite evidence of chloroquine resistance. Here, Auburn et al. compare population structure of P. vivax in Malaysia to regions with intermediate and high transmission and identify genetic regions under putative selection.
- Sarah Auburn
- , Ernest D. Benavente
- & Ric N. Price
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| Open AccessWild bonobos host geographically restricted malaria parasites including a putative new Laverania species
Unlike chimpanzees and gorillas, bonobos have not been found infected by malaria parasites in the wild. Here, Liu et al. report more thorough survey and sequencing results showing that bonobos host malaria parasites, including a yet-unknown species, but only in the eastern-most part of their range.
- Weimin Liu
- , Scott Sherrill-Mix
- & Beatrice H. Hahn
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| Open AccessGenomes of cryptic chimpanzee Plasmodium species reveal key evolutionary events leading to human malaria
African apes harbour six Plasmodium species, one of which gave rise to the human malaria parasite. Here, Sundaraman et al. use selective whole-genome amplification to determine genome sequences from two chimpanzee Plasmodiumspecies, shedding light on the evolutionary origin of the human parasite.
- Sesh A. Sundararaman
- , Lindsey J. Plenderleith
- & Beatrice H. Hahn
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| Open AccessThe Opisthorchis viverrini genome provides insights into life in the bile duct
The Asian liver fluke is a parasitic worm that is linked to an increased risk of malignant cancer. Here, the authors sequence the draft genome and transcriptome of this fluke and provide insight into how the species has adapted to be able to survive in the bile duct.
- Neil D. Young
- , Niranjan Nagarajan
- & Robin B. Gasser
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| Open AccessA barcode of organellar genome polymorphisms identifies the geographic origin of Plasmodium falciparum strains
Tracing the source of malarial infections is an important step towards monitoring and controlling the disease. Here, Preston et al. analyse sequence data from 711 isolates and design a genetic barcode based on combined mitochondrial and apicoplast genomes that is able to distinguish between malaria parasites isolated from different geographical regions.
- Mark D. Preston
- , Susana Campino
- & Taane G. Clark