Parasite biology

  • Article | | open

    Schizogony is essential for blood stage infection of Plasmodium parasites and produces several daughter cells. Here, Rudlaff et al. identify PfCINCH and interacting proteins as essential components of the basal complex required to establish daughter cell boundaries.

    • Rachel M. Rudlaff
    • , Stephan Kraemer
    • , Vincent A. Streva
    •  & Jeffrey D. Dvorin
  • Article | | open

    Gastrointestinal infection with parasitic helminths can protect against mucosal diseases via impacting on the microbiome. Here the authors show that ES-62, a product secreted by a tissue-resident helminth modulates the host gut microbiome to protect against inflammatory arthritis in a mouse model.

    • James Doonan
    • , Anuradha Tarafdar
    • , Miguel A. Pineda
    • , Felicity E. Lumb
    • , Jenny Crowe
    • , Aneesah M. Khan
    • , Paul A. Hoskisson
    • , Margaret M. Harnett
    •  & William Harnett
  • Article | | open

    Protein kinase A (PKA) is typically activated by cAMP. Here, Bachmaier et al. show that PKA of Trypanosoma is activated by nucleoside-related ligands, explain the ligand selectivity swap by a co-crystal structure of trypanosome PKAR, and identify potential downstream targets by phosphoproteomics.

    • Sabine Bachmaier
    • , Yuri Volpato Santos
    • , Susanne Kramer
    • , George Boniface Githure
    • , Thomas Klöckner
    • , Julia Pepperl
    • , Cordula Baums
    • , Robin Schenk
    • , Frank Schwede
    • , Hans-Gottfried Genieser
    • , Jean-William Dupuy
    • , Ignasi Forné
    • , Axel Imhof
    • , Jerôme Basquin
    • , Esben Lorentzen
    •  & Michael Boshart
  • Article | | open

    Trypanosoma brucei probably relies on chemotactic signals for movement through tsetse fly tissues, but the molecular basis is unknown. Here, the authors show that flagellar cAMP signaling is required for traversal of the peritrophic matrix and that, without it, parasites are trapped in the midgut lumen.

    • Sebastian Shaw
    • , Stephanie F. DeMarco
    • , Ruth Rehmann
    • , Tanja Wenzler
    • , Francesca Florini
    • , Isabel Roditi
    •  & Kent L. Hill
  • Article | | open

    Cortical microtubules of Toxoplasma gondii are exceptionally stable, but it isn’t known how they are anchored along membranes. Here, Harding et al. show that GAPM proteins localize to the inner membrane complex and are essential for maintaining the structural stability of parasites.

    • Clare R. Harding
    • , Matthew Gow
    • , Joon Ho Kang
    • , Emily Shortt
    • , Scott R. Manalis
    • , Markus Meissner
    •  & Sebastian Lourido
  • Article | | open

    Plasmodium vivax biology is not well understood, due to a lack of in vitro culture systems and difficulties associated with studying clinical blood samples. Here, Kim et al. use gene expression profiles from P. vivax infected patient blood and show stage-specific chloroquine response and differential regulation of male and female gametocytes.

    • Adam Kim
    • , Jean Popovici
    • , Didier Menard
    •  & David Serre
  • Article | | open

    Polyadenylation stabilizes edited mitochondrial mRNAs in Trypanosoma brucei, but the involved poly(A) binding protein is unknown. Here, Mesitov et al. show that a pentatricopeptide repeat factor KPAF4 binds to A-tail and prevents exonucleolytic degradation as well as translation of incompletely edited mRNAs.

    • Mikhail V. Mesitov
    • , Tian Yu
    • , Takuma Suematsu
    • , Francois M. Sement
    • , Liye Zhang
    • , Clinton Yu
    • , Lan Huang
    •  & Inna Aphasizheva
  • Article | | open

    Trypanosoma brucei mainly relies on translational regulation to adjust gene expression, but details are unclear. Here the authors show that, under stress conditions, tRNAThr half level increases, associates with ribosomes and polysomes, and stimulates protein synthesis by facilitating mRNA loading.

    • Roger Fricker
    • , Rebecca Brogli
    • , Hannes Luidalepp
    • , Leander Wyss
    • , Michel Fasnacht
    • , Oliver Joss
    • , Marek Zywicki
    • , Mark Helm
    • , André Schneider
    • , Marina Cristodero
    •  & Norbert Polacek
  • Article | | open

    Despite functional optimisation during evolution of parasitism, most members of a calcium dependent protein kinase (CDPK) family show genetic redundancy in Plasmodium. Here, the authors screen 294 genetic interactions among protein kinases in Plasmodium and show how some CDPKs functionally interact to control motility and host cell invasion.

    • Hanwei Fang
    • , Ana Rita Gomes
    • , Natacha Klages
    • , Paco Pino
    • , Bohumil Maco
    • , Eloise M. Walker
    • , Zenon A. Zenonos
    • , Fiona Angrisano
    • , Jake Baum
    • , Christian Doerig
    • , David A. Baker
    • , Oliver Billker
    •  & Mathieu Brochet
  • Article | | open

    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
    • , Sachel Mok
    • , Tomas Yeo
    • , Kathryn J. Wicht
    • , Krittikorn Kümpornsin
    • , Shannon Takala-Harrison
    • , Benoit Witkowski
    • , Rick M. Fairhurst
    • , Frederic Ariey
    • , Didier Menard
    •  & David A. Fidock
  • Article | | open

    Mosquito saliva can affect transmission of Plasmodium to mammalian hosts, but active saliva components or mechanisms are poorly understood. Here, the authors identify a mosquito saliva protein that binds Plasmodium sporozoites and inhibits cell traversal in vitro and sporozoite speed in mice.

    • Tyler R. Schleicher
    • , Jing Yang
    • , Marianna Freudzon
    • , Alison Rembisz
    • , Samuel Craft
    • , Madeleine Hamilton
    • , Morven Graham
    • , Godfree Mlambo
    • , Abhai K. Tripathi
    • , Yue Li
    • , Peter Cresswell
    • , Photini Sinnis
    • , George Dimopoulos
    •  & Erol Fikrig
  • Article | | open

    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
    • , Aswathy Sebastian
    • , Istvan Albert
    • , John D. Storey
    •  & Manuel Llinás
  • Article | | open

    Apicomplexan parasites such as Toxoplasma gondii possess a tubulin-rich structure called the conoid. Here, Long et al. identify a conoid protein that interacts with motor and structural proteins and is required for structural integrity of the conoid, parasite motility, and host cell invasion.

    • Shaojun Long
    • , Bryan Anthony
    • , Lisa L. Drewry
    •  & L. David Sibley
  • Article | | open

    Invasion of red blood cells by Plasmodium falciparum is a complex process and relies on several receptor-ligand interactions. Here, the authors show that human cyclophilin B binds Plasmodium surface protein PfRhopH3 and that interruption of this interaction reduces invasion by 80%.

    • Prem Prakash
    • , Mohammad Zeeshan
    • , Ekta Saini
    • , Azhar Muneer
    • , Sachin Khurana
    • , Bishwanath Kumar Chourasia
    • , Arunaditya Deshmukh
    • , Inderjeet Kaur
    • , Surabhi Dabral
    • , Niharika Singh
    • , Zille Anam
    • , Ayushi Chaurasiya
    • , Shikha Kaushik
    • , Pradeep Dahiya
    • , Md. Kalamuddin
    • , Jitendra Kumar Thakur
    • , Asif Mohmmed
    • , Anand Ranganathan
    •  & Pawan Malhotra
  • Article | | open

    The role of O-glycosylation in the malaria life cycle is largely unknown. Here, the authors identify a Plasmodium protein O-fucosyltransferase and show that it is important for normal trafficking of a subset of surface proteins, particularly CSP and TRAP, and efficient infection of mosquito and vertebrate hosts.

    • Sash Lopaticki
    • , Annie S. P. Yang
    • , Alan John
    • , Nichollas E. Scott
    • , James P. Lingford
    • , Matthew T. O’Neill
    • , Sara M. Erickson
    • , Nicole C. McKenzie
    • , Charlie Jennison
    • , Lachlan W. Whitehead
    • , Donna N. Douglas
    • , Norman M. Kneteman
    • , Ethan D. Goddard-Borger
    •  & Justin A. Boddey
  • Article | | open

    Plasmodium-infected red blood cells export virulence factors, such as PfEMP1, to the cell surface. Here, the authors identify a protein complex termed EPIC that interacts with PfEMP1 during export, and they show that knockdown of an EPIC component affects parasite virulence.

    • Steven Batinovic
    • , Emma McHugh
    • , Scott A. Chisholm
    • , Kathryn Matthews
    • , Boiyin Liu
    • , Laure Dumont
    • , Sarah C. Charnaud
    • , Molly Parkyn Schneider
    • , Paul R. Gilson
    • , Tania F. de Koning-Ward
    • , Matthew W. A. Dixon
    •  & Leann Tilley
  • Article | | open

    Calcium dependent protein kinase 1 (CDPK1) plays an important role in asexual development of Plasmodium falciparum. Using phosphoproteomics and conditional knockdown of CDPK1, the authors here identify CDPK1 substrates and a cross-talk between CDPK1 and PKA, and show the role of CDPK1 in parasite invasion.

    • Sudhir Kumar
    • , Manish Kumar
    • , Roseleen Ekka
    • , Jeffrey D. Dvorin
    • , Aditya S. Paul
    • , Anil K. Madugundu
    • , Tim Gilberger
    • , Harsha Gowda
    • , Manoj T. Duraisingh
    • , T. S. Keshava Prasad
    •  & Pushkar Sharma
  • Article | | open

    The mechanism by which Toxoplasma gondii achieves synchronized cell division is incompletely understood. Here, the authors identify an intravacuolar cell-cell communication that ensures synchronized division and depends on myosin I.

    • Karine Frénal
    • , Damien Jacot
    • , Pierre-Mehdi Hammoudi
    • , Arnault Graindorge
    • , Bohumil Maco
    •  & Dominique Soldati-Favre
  • Article | | open

    The secreted Plasmodium falciparum protein RH5 is essential for invasion of erythrocytes and is a promising vaccine candidate. Here, Galaway et al. show that the N-terminal region of RH5 binds the GPI-anchored merozoite surface protein P113 and can elicit invasion-blocking antibodies.

    • Francis Galaway
    • , Laura G. Drought
    • , Maria Fala
    • , Nadia Cross
    • , Alison C. Kemp
    • , Julian C. Rayner
    •  & Gavin J. Wright
  • Article | | open

    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
    • , Tomasino Pace
    • , Leonardo Picci
    • , Giulia Peruzzi
    • , Vassiliki Varamogianni-Mamatsi
    • , Lefteris Spanos
    • , Célia R. S. Garcia
    • , Roberta Spaccapelo
    • , Marta Ponzi
    •  & Inga Siden-Kiamos
  • Article | | open

    Targeting of the CD36 scavenger receptor by the malaria parasite effector PfEMP1 prevents splenic clearance of infected erythrocytes. Here, the authors propose that diverse PfEMP1 achieve this by binding to a conserved phenylalanine residue in CD36 that is also required for lipoprotein binding.

    • Fu-Lien Hsieh
    • , Louise Turner
    • , Jani Reddy Bolla
    • , Carol V. Robinson
    • , Thomas Lavstsen
    •  & Matthew K. Higgins
  • Article | | open

    It is unclear whether new antimalarial compounds may rapidly lose effectiveness in the field because of parasite resistance. Here, Corey et al. investigate the acquisition of drug resistance and the extent to which common resistance mechanisms decrease susceptibility to a diverse set of 50 antimalarial compounds.

    • Victoria C. Corey
    • , Amanda K. Lukens
    • , Eva S. Istvan
    • , Marcus C. S. Lee
    • , Virginia Franco
    • , Pamela Magistrado
    • , Olivia Coburn-Flynn
    • , Tomoyo Sakata-Kato
    • , Olivia Fuchs
    • , Nina F. Gnädig
    • , Greg Goldgof
    • , Maria Linares
    • , Maria G. Gomez-Lorenzo
    • , Cristina De Cózar
    • , Maria Jose Lafuente-Monasterio
    • , Sara Prats
    • , Stephan Meister
    • , Olga Tanaseichuk
    • , Melanie Wree
    • , Yingyao Zhou
    • , Paul A. Willis
    • , Francisco-Javier Gamo
    • , Daniel E. Goldberg
    • , David A. Fidock
    • , Dyann F. Wirth
    •  & Elizabeth A. Winzeler
  • Article | | open

    It is unknown whether artemisinin-resistant malaria parasites from Southeast Asia can infect any African species of Anopheles mosquitoes and thus spread to Africa. Here, St. Laurent et al. show that artemisinin-resistant isolates from Cambodia can indeed infect the major African vector, Anopheles coluzzii.

    • Brandyce St. Laurent
    • , Becky Miller
    • , Timothy A. Burton
    • , Chanaki Amaratunga
    • , Sary Men
    • , Siv Sovannaroth
    • , Michael P. Fay
    • , Olivo Miotto
    • , Robert W. Gwadz
    • , Jennifer M. Anderson
    •  & Rick M. Fairhurst
  • Article | | open

    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 Plasmodium species 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
    • , Weimin Liu
    • , William R. Proto
    • , Aaron Clauset
    • , Dorothy E. Loy
    • , Sheri Speede
    • , Lindsey J. Plenderleith
    • , Paul M. Sharp
    • , Beatrice H. Hahn
    • , Julian C. Rayner
    •  & Caroline O. Buckee
  • Article | | open

    Mice engrafted with human cells are useful models for research on human malaria parasites. Here the authors show that the complete life cycle of Plasmodium falciparum and the liver stages of Plasmodium ovale can be studied in mice doubly engrafted with human primary hepatocytes and red blood cells.

    • Valérie Soulard
    • , Henriette Bosson-Vanga
    • , Audrey Lorthiois
    • , Clémentine Roucher
    • , Jean- François Franetich
    • , Gigliola Zanghi
    • , Mallaury Bordessoulles
    • , Maurel Tefit
    • , Marc Thellier
    • , Serban Morosan
    • , Gilles Le Naour
    • , Frédérique Capron
    • , Hiroshi Suemizu
    • , Georges Snounou
    • , Alicia Moreno-Sabater
    •  & Dominique Mazier
  • Article | | open

    Protein kinases expressed by the malaria parasite Plasmodium falciparum represent potentially valuable drug targets. Alam et al. identify proteins whose phosphorylation is dependent on the kinase PfPKG, revealing a regulatory network controlling parasite egress from red blood cells and calcium signalling.

    • Mahmood M. Alam
    • , Lev Solyakov
    • , Andrew R. Bottrill
    • , Christian Flueck
    • , Faiza A. Siddiqui
    • , Shailja Singh
    • , Sharad Mistry
    • , Maria Viskaduraki
    • , Kate Lee
    • , Christine S. Hopp
    • , Chetan E. Chitnis
    • , Christian Doerig
    • , Robert W. Moon
    • , Judith L. Green
    • , Anthony A. Holder
    • , David A. Baker
    •  & Andrew B. Tobin
  • Article |

    Malaria parasites generate metabolic energy through anaerobic glycolysis, yielding lactate and protons that are then secreted out of the parasite cell by an unknown transporter. Here, the authors identify and characterize a lactate/proton transporter that may be carrying out such function in Plasmodium.

    • Binghua Wu
    • , Janis Rambow
    • , Sinja Bock
    • , Julia Holm-Bertelsen
    • , Marie Wiechert
    • , Alexandra Blancke Soares
    • , Tobias Spielmann
    •  & Eric Beitz
  • Article | | open

    Understanding the epidemiology of malaria transmission between humans and mosquitoes is crucial for successful disease control. Analysing data from an 18-year malaria control programme, Churcher et al. show that decreased parasite prevalence in humans can be found concurrently with an increase in transmission efficiency.

    • Thomas S. Churcher
    • , Jean-François Trape
    •  & Anna Cohuet
  • Article | | open

    Plasmodium falciparum reticulocyte-binding protein homologue 1 (PfRH1) and erythrocyte-binding-like protein EBA175 are important for parasite invasion of host cells. Here, Gao et al. show that PfRH1 activates calcium signalling, which induces release of EBA175 and allows junction formation between host cell and parasite.

    • Xiaohong Gao
    • , Karthigayan Gunalan
    • , Sally Shu Lin Yap
    •  & Peter R. Preiser
  • Article |

    Actin normally polymerizes into filaments in a cooperative manner, with nucleation and elongation phases. Skillman et al. show that actin from the protozoan parasite Toxoplasma gondii polymerizes in an isodesmic manner, without any evidence of nucleation, resulting in filaments that are very short and unstable.

    • Kristen M. Skillman
    • , Christopher I. Ma
    • , Daved H. Fremont
    • , Karthikeyan Diraviyam
    • , John A. Cooper
    • , David Sept
    •  & L. David Sibley
  • Article |

    The number of human infections caused by the primate malaria parasite P. knowlesi is increasing. Lim et al. demonstrate that host specificity is due to the preference of the parasite for young blood cells, and that the parasite can adapt to proliferate in human blood containing a range of differently aged cells.

    • Caeul Lim
    • , Elsa Hansen
    • , Tiffany M. DeSimone
    • , Yovany Moreno
    • , Klara Junker
    • , Amy Bei
    • , Carlo Brugnara
    • , Caroline O. Buckee
    •  & Manoj T. Duraisingh
  • Article |

    The proteome of the malarial parasite Plasmodium falciparum has an overabundance of aggregation-prone asparagine repeat-containing proteins. Muralidharan et al. show that Plasmodium Hsp110 protein potently prevents aggregation of asparagine-rich proteins, thereby allowing the parasite to survive febrile episodes.

    • Vasant Muralidharan
    • , Anna Oksman
    • , Priya Pal
    • , Susan Lindquist
    •  & Daniel E. Goldberg
  • Article | | open

    Malaria can persist at levels that escape detection by standard microscopy, but can be detected by PCR. Okell et al. now show that rates of submicroscopic infection can be predicted using more widely available microscopy data, and are most epidemiologically significant in areas with low malaria transmission.

    • Lucy C. Okell
    • , Teun Bousema
    • , Jamie T. Griffin
    • , André Lin Ouédraogo
    • , Azra C. Ghani
    •  & Chris J. Drakeley
  • Article |

    The Plasmodium falciparum parasite that causes malaria has a complex life cycle in human erythrocytes. Using time-lapse three-dimensional imaging, the authors show the intraerythrocytic stages of the parasite and provide new insight into the export of P. falciparum proteins to Maurer's clefts.

    • Christof Grüring
    • , Arlett Heiber
    • , Florian Kruse
    • , Johanna Ungefehr
    • , Tim-Wolf Gilberger
    •  & Tobias Spielmann