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| 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
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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
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| 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
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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
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| 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
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| 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
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| 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 AccessMark-release-recapture experiment in Burkina Faso demonstrates reduced fitness and dispersal of genetically-modified sterile malaria mosquitoes
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
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| Open AccessGenotyping cognate Plasmodium falciparum in humans and mosquitoes to estimate onward transmission of asymptomatic infections
Asymptomatic malaria infections contribute to transmission. Here, Sumner et al. infer participant-to-mosquito transmission by sampling naturally-fed mosquitoes from households in Western Kenya and find that asymptomatic infections more than double the odds of transmission to a mosquito compared to symptomatic infections.
- Kelsey M. Sumner
- , Elizabeth Freedman
- & Steve M. Taylor
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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 AccessPlasmodium vivax chloroquine resistance links to pvcrt transcription in a genetic cross
Here, a cross of Plasmodium vivax malaria parasites links a chloroquine resistance (CQR) phenotype to a 76 kb region of chromosome 1 and greater expression of pvcrt, an ortholog of the Plasmodium falciparum CQR transporter gene.
- Juliana M. Sá
- , Sarah R. Kaslow
- & Thomas E. Wellems
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| Open AccessA CRISPR platform for targeted in vivo screens identifies Toxoplasma gondii virulence factors in mice
Targeted CRISPR libraries expand the use of genetic screens across experimental conditions. Here, the authors develop a method for generating and analysing small scale custom CRISPR libraries and use it in the human and livestock pathogen Toxoplasma gondii to identify virulence factors in mice.
- Joanna Young
- , Caia Dominicus
- & Moritz Treeck
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| Open AccessMonoallelic expression and epigenetic inheritance sustained by a Trypanosoma brucei variant surface glycoprotein exclusion complex
Monoallelic expression of variant surface glycoprotein genes (VSGs) is essential for immune evasion by Trypanosoma brucei. Here, Faria et al. show that the VEX protein complex controls VSG allelic exclusion, and that CAF‐1 sustains inheritance of the VEX‐complex in association with the active VSG.
- Joana Faria
- , Lucy Glover
- & David Horn
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| Open AccessDual RNA-seq identifies human mucosal immunity protein Mucin-13 as a hallmark of Plasmodium exoerythrocytic infection
Host-parasite interactions during the exoerythrocytic stage of Plasmodium infection remains poorly understood. Using dual RNA-Seq, the authors show that human mucosal immunity protein mucin-13 is upregulated during Plasmodium hepatic-stage infection and marks infected cells independent of tested Plasmodium species.
- Gregory M. LaMonte
- , Pamela Orjuela-Sanchez
- & Elizabeth A. Winzeler
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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 AccessA Plasmodium yoelii HECT-like E3 ubiquitin ligase regulates parasite growth and virulence
Many strains of Plasmodium differ in virulence, but factors that control these distinctions are not known. Here the authors comparatively map virulence loci using the offspring from a P. yoelii YM and N67 genetic cross, and identify a putative HECT E3 ubiquitin ligase that may explain the variance.
- Sethu C. Nair
- , Ruixue Xu
- & Xin-zhuan Su
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| Open AccessGlobally prevalent PfMDR1 mutations modulate Plasmodium falciparum susceptibility to artemisinin-based combination therapies
Antimalarial chemotherapy relies on combination therapies (ACTs) consisting of an artemisinin derivative and a partner drug. Here, the authors study the effects of globally prevalent mutations in a multidrug resistance transporter (PfMDR1) on the parasite’s susceptibility to ACT drugs.
- M. Isabel Veiga
- , Satish K. Dhingra
- & David A. Fidock
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| Open AccessSynthetic RNA–protein modules integrated with native translation mechanisms to control gene expression in malaria parasites
Current strategies for regulatory control of gene expression are orthogonal to the host organism mechanisms. Here the authors demonstrate an RNA aptamer controlled system integrated into native regulatory pathways in the parasite Plasmodium falciparum.
- Suresh M. Ganesan
- , Alejandra Falla
- & Jacquin C. Niles
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| Open AccessFunctional 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 AccessLocal admixture of amplified and diversified secreted pathogenesis determinants shapes mosaic Toxoplasma gondii genomes
Toxoplasma gondii is a parasite that causes zoonotic infections in humans. Here, the authors identify tandem amplification and diversification of secretory pathogenesis determinants in the T. gondiigenome and show that clade-specific inheritance of conserved haploblocks enriched for these determinants shapes population structure.
- Hernan Lorenzi
- , Asis Khan
- & L. David Sibley
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| Open AccessApe parasite origins of human malaria virulence genes
Antigens encoded by var genes are major virulence factors of the human malaria parasite Plasmodium falciparum. Here, Larremore et al. identify var-like genes in distantly related Plasmodiumspecies infecting African apes, indicating that these genes already existed in an ancestral ape parasite many millions of years ago.
- Daniel B. Larremore
- , Sesh A. Sundararaman
- & Caroline O. Buckee
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| Open AccessCaenorhabditis elegans is a useful model for anthelmintic discovery
Screening for new anthelmintic compounds that are active against parasitic nematodes is costly and labour intensive. Here, the authors use the non-parasitic nematode Caenorhabditis elegansto identify 30 anthelmintic lead compounds in an effective and cost-efficient manner.
- Andrew R. Burns
- , Genna M. Luciani
- & Peter J. Roy
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| Open AccessLucilia cuprina genome unlocks parasitic fly biology to underpin future interventions
Lucilia cuprina is a parasitic blowfly of major economic importance worldwide that feeds on the tissues of animals such as sheep. Here, the authors sequence the genome of L. cuprinaand provide insights into the fly’s molecular biology, interactions with the host animal and insecticide resistance.
- Clare A. Anstead
- , Pasi K. Korhonen
- & Robin B. Gasser
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| Open AccessGenetic blueprint of the zoonotic pathogen Toxocara canis
Toxocara canis is a zoonotic parasite of major worldwide socioeconomic importance. Here, the authors sequence the genome and transcriptome of T. canis, and highlight potential mechanisms involved in development and host–parasite interactions that could support the pursuit of new drug interventions.
- Xing-Quan Zhu
- , Pasi K. Korhonen
- & Robin B. Gasser
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| Open AccessSir2a regulates rDNA transcription and multiplication rate in the human malaria parasite Plasmodium falciparum
The factors that modulate growth rate of the human malaria parasite Plasmodium falciparum remain poorly understood. Here Scherf and collaborators demonstrate that the Plasmodiumsirtuin PfSir2a regulates the transcription of ribosomal DNA, thereby modulating parasite proliferation rate and virulence.
- Liliana Mancio-Silva
- , Jose Juan Lopez-Rubio
- & Artur Scherf